After having a vision of Chaos rising and Apophis returning, magician Ruby Kane and her husband Julius set out to stop Apophis from returning. To this end, Ruby communicated with the goddess Isis who told her that the first step to restoring the gods and stopping Apophis would be to release Bast from Apophis’ prison where she was battling him for eternity, but slowly losing. Ruby and Julius released Bast, but Ruby sacrificed herself to seal the gate they opened so that Apophis could not follow Bast through. Julius then made a deal with Bast wherein she was allowed to remain in the mortal world in exchange for Bast taking on the minor form of the cat Muffin and protecting Julius’ daughter Sadie, a deal which Bast agreed to. As a result of his illegal actions, Julius was exiled from the House of Life which separated Sadie and her brother Carter, fearing they would become too powerful if allowed to grow up together. As a result, Carter traveled the world with his father while Sadie lived in London with her grandparents Mr. and Mrs. Faust.
Determined to continue his and Ruby’s work, Julius spent the next six years working on a way to summon Osiris in order to restore him to his proper place in the Underworld as a first step to restoring Ma'at. On Christmas Eve, Julius finally discovers a way using the Rosetta Stone and enlists his children’s help to keep the curator of the British Museum busy while he performs the spell. Unaware of just how much power is stored in the Rosetta Stone, Julius inadvertently destroys it and releases not just Osiris, but also Set, Nephthys, Horus and Isis as well. Set quickly defeats Julius in combat and imprisons him and Osiris, who takes Julius as his host after being released, in a golden sarcophagus. Horus and Isis take Carter and Sadie as hosts respectively, unknown to them and the two gods protect the young magicians and Set flees when Michel Desjardins and Zia Rashid, who is taken as a host by Nephthys, arrive. Due to the destruction caused by the explosion of the Rosetta Stone, Julius is suspected to be a terrorist and his children are questioned about his activities before their uncle Amos uses magic to make the chief inspector deport them instead and Amos takes them to Brooklyn House in the Twenty-First Nome in New York. At the same time, Chief Lector Iskandar discovers Zia’s possession by Nephthys and replaces her with a shabti in secret to protect her from the House of Life while hiding the real Zia in a tomb at her old village.
That night, due to Carter not using an enchanted headrest, his ba travels to where Set meets with two demons, one whom, Face of Horror, is secretly possessed by Apophis to use Set to free Apophis from his prison. Carter witnesses Set discuss his plan to build a temple on Camelback Mountain near Phoenix, Arizona and use it to unleash “the greatest storm ever known” on his birthday. Carter also witnesses Set ordering Face of Horror to send out their forces to capture the “younglings” and to start with the “longnecks.” After waking up, Carter joins Sadie and Amos for breakfast where Amos explains some of the history of the House of Life, the Egyptian gods, magicians and their family and its role as well as the fact that Julius summoned Osiris to presumably bring back their mother. After Carter informs Amos of his dream and what Set said, Amos departs to find out more without giving Carter or Sadie any real answers and ordering them to stay out of Brooklyn House’s library. Unknown to them, Amos is in fact possessed by Set and he sabotages Brooklyn House’s defenses under Set’s control so Set’s forces can get at Carter and Sadie.
After Amos’ departure, the Kanes enter the library for answers. There, they find a scroll called Blood of the Pharaohs which reveals they are descendants of the Pharaohs and the story about the Demon Days and the gods related to it. Carter and Sadie realize that they are facing Set and that he will be setting off his storm on his birthday and their father had expected them to stop Set. Before they can investigate further for more clues, they are interrupted by a crash in the Great Room and rush to see what’s wrong.
Reaching the Great Room, the Kanes find Khufu going crazy and two serpopards attacking the outmatched Philip of Macedonia in the pool. Though Sadie tries to go help Phillip, Carter stops her as Amos had told them that the house was protected by magic and they were safe inside. As the two watch, Phillip lifts himself up into the air, starts to glow and then slams back down with enough force to break off part of the terrace and send Phillip and the serpopards falling into the East River, apparently killing all three. Carter realizes that the serpopards might not be dead and he and Sadie return to the library where Carter has a retrieval shabti retrieve the Narmer Palette which depicts the serpopards. Carter realizes that the serpopards are the “longnecks” Set mentioned sending after them and they return to the Great Room after hearing crashing to find the serpopards back and trying to break into the mansion. Though Khufu tries to signal Sadie to ask Muffin for help, Sadie doesn’t get it and the serpopards continue their work unimpeded. After searching, the serpopards locate the sabotaged wards on one of the doors and begin working on breaking the door down with the warding failing after only two hits. While Sadie suggests trying the ha-di spell on the monsters, Carter refuses the idea as using the spell nearly caused Sadie to pass out the last time and trying again could potentially have the same effect or worse. For a lack of a better idea, Carter retrieves a khopesh sword from one of the wall displays to attempt to defend them with. With their third hit, the serpopards are able to break through the glass door, causing Khufu to hit one with his basketball and then jump on its back and sink his fangs into its neck in an attempt to kill the monster. However, the monster retaliates and knocks Khufu off the terrace to his apparent death like Philip of Macedonia. Cornered, Sadie remembers Amos telling her that Muffin will protect them and in desperation orders Muffin to protect her and Carter. While nothing seems to happen at first, Sadie’s order to protect them allows Bast to resume human form to aid the Kanes. The serpopards attack Bast, but she dodges their attack, lands on the mantle and draws her two knives. Bast jumps between the monsters who attempt to attack her, but Bast is able to dodge the serpopards attacks and lash their necks together. While the serpopards are stuck together, Bast uses her knives to decapitate the monsters, killing them. Bast then tells the shocked Sadie and Carter that they need to leave as worse will be coming and asks Sadie to open a portal. However, Sadie can’t do it so Bast decides to take them to an obelisk in Central Park in Manhattan to help them out. Carter realizes who Bast is and while Sadie wants to search for Phillip and Khufu, Bast insists they will be fine and they have to leave as Brooklyn House’s defenses have been sabotaged and it is no longer safe there as only a magician could’ve done it. Finally, Bast drags Carter and Sadie out of Brooklyn House to flee to safety.
Outside, Bast encounters an old tomcat who she orders to spread the word of their plight to all of the cats in New York so the cats can help them. After Bast destroys a wrecking ball, Brooklyn House catches fire and they quickly steal a Lexus convertible to drive to the obelisk in Central Park. While Carter hesitates about using a stolen car, after they spot four carriers coming after them, he stops hesitating and they flee in the car. Using her cat-like reflexes, Bast is able to drive the three of them through Brooklyn traffic at insane speeds and onto the Williamsburg Bridge without causing an accident though the carriers are able to follow them even at that speed. Carter questions Bast on the nature of the carriers and why even though she’s a goddess, she can’t just easily destroy them or teleport herself and the Kanes to safety. Bast explains that in the form of Muffin, she’s limited in what she can do and even in a powerful host, she’s no match for Set’s power. As the Kanes try to understand the situation, Bast explains her deal with their father to be able to stay in the mortal world in exchange for protecting Sadie and Carter realizes that it was when she released Bast that their mother died. However, Bast refuses to go further into the subject and tells them that they need to get out of New York and summon more gods to help them fight Set. After reaching Manhattan and with the carriers still closing in, Bast summons an army of cats to attack the carriers and buy them some time to get away. Reaching the Metropolitan Museum of Art, the three ditch the stolen car and race to the nearby obelisk where Bast tells Sadie to open a portal to the Duat for them to escape through. Bast explains to Sadie that she’s not good at opening portals herself and they need to escape before Set summon more gods to his cause. A Siamese cat arrives and warns Bast that the carriers are coming and something else the cat has trouble describing is coming from the east. Bast realizes that the carriers master has grown impatient and warns the Kanes that it’s likely another god that’s a minion or ally of Set’s. As the carriers, battered from the attack by the cats arrive, Bast tells Sadie to get the portal open while she deals with them and tells Carter he can help her if he wants. Bast summons her combat avatar, impressing Carter as she attacks the carriers, slashing one apart with her claws and stomping another flat. As Bast continues battling the carriers and Sadie continues to try to summon a portal, Carter decides to help Bast and draws his khopesh. As Carter rushes to Bast’s aid, she slices the last two carriers apart, apparently killing them and leaving Carter relieved. However, the carriers quickly reform and Bast calls to Carter to help by slicing them into smaller pieces once she’s disabled them. Bast then begins slicing and stomping carriers again and once they are disabled, Carter uses his sword to slice them into tiny pieces. Together, Carter and Bast kill the carriers, leaving Carter wondering why they ran when the fight was so easy. However, Carter then realizes that the fight exhausted Bast and realizes that using her combat avatar drew more energy than he had realized. After killing the carriers, Bast checks with Sadie on how her opening a portal is going only to learn that it’s not going well. At that moment, thousands of scorpions arrive followed by the scorpion goddess Serqet. When Sadie still can’t open a portal, Bast orders them to run to the museum and find “the temple” which might protect them while she holds Serqet off. Though she tells them she’ll be fine, Carter can tell Bast doesn’t really believe it and is just buying them time. However, Carter follows her orders and takes Sadie and runs while Bast faces the army of scorpions. Bast begins smashing scorpions with her fists and feet, killing hundreds of them, but there are too many for her to beat and they start wriggling into Bast’s combat avatar, draining its energy. Eventually, the scorpions reduce Bast’s energy to almost nothing, but she uses the last of her power to return to the form of Muffin and escape through the Duat to safety.
As Bast struggles against Serqet’s scorpions, Carter and Sadie race to the Metropolitan Museum of Art where they quickly hide from security before starting to search for the temple Bast mentioned. As the two search, the museum’s alarms go off and they hear Serqet’s scorpions and start to worry for their friend’s safety. The two desperately search for the temple, but get lost before running into Zia Rashid. Though the Kanes are suspicious of Zia at first due to her wanting to kill them after their father released the gods, they are forced to trust her due to the approach of Serqet and her scorpions. Zia leads them to the Temple of Dendur inside the museum where she activates a hieroglyph that will open a portal the next time it’s possible to open one. However, they have to hold on for ten and a half minutes before they can open a portal and Zia has Sadie set up the Four Sons of Horus and Carter a protection circle to help them survive Serqet long enough to escape. While the Kanes express fear that Zia can’t defeat Serqet due to Bast falling to her, Zia tells them that she’s a scribe in the House of Life trained to fight gods. Moments later, Serqet enters and demands that Zia hand over the Kanes but Zia simply proclaims that she’s a Scribe of the First Nome and demands Serqet leave or be destroyed. Serqet sends her scorpion army at them, but the protective circle fries the first scorpion to touch it and the rest retreat into Serqet’s robes. Serqet then forms a shadowy scorpion around herself and sent her massive shadowy scorpion tail at Zia who deflects it with her wand. Zia blasts Serqet with fire from her staff, but angers the goddess more than she hurts her. As the goddess mocks her, Zia throws her wand at Serqet’s shadowy scorpion tail, causing a blinding flash of light that distracts the goddess before Zia jumps from her protective circle to battle Serqet. As Zia leaves the circle, the portal opens, but Zia ignores it in favor of continuing her fight with the goddess. Sadie nearly leaves the protection circle to join the fight, but is stopped by Carter who brings Sadie back to her senses. As Zia distracts Serqet by caging her with fire, Zia releases the Seven Ribbons of Hathor which pass through Serqet’s shadow scorpion and bind her, destroying the shadow scorpion. Causing the Ribbons to glow, Zia demands that Serqet release her host and forces Serqet to the ground when she refuses, knocking the goddess out. As Carter tries to warn Zia that the portal is closing, Zia touches Serqet on the forehead and exorcises the goddess from her host. However, Serqet’s essence quickly starts to reform rather than dissipate as the Seven Ribbons of Hathor should’ve forced her to, leaving Zia shocked. As Serqet’s essence forms into a two-story tall scorpion, Carter warns Zia once again that the portal is closing and they need to go. Seeing no other option, Zia flees with Carter and Sadie through the portal to safety.
Following their escape through the portal, Zia takes the Kanes to the First Nome where Chief Lector Iskandar spares their lives at Zia’s request despite Michel Desjardins objections. The next day, Zia begins training the Kanes, but they are forced to flee through another portal to Paris after Iskandar dies and Desjardins becomes Chief Lector and orders their death. In Paris, the Kanes are reunited with Bast who they had believed died in battle with Serqet and her scorpions and set out to defeat Set and rescue their father. The Kanes later encounter both Philip of Macedonia and Khufu who survived the attack as well and aid them in their quest. While Brooklyn House was destroyed by the carriers, it is later repaired by the gods as part of a thank-you gift for defeating Set.