The Quest to the Doors of Death was undertaken by the crew of the Argo II in Greece, while Percy Jackson, Annabeth Chase, and Iapetus journeyed across Tartarus so that the Doors could be simultaneously closed from both sides.
While the quest had no accompanying prophecy, it fulfilled a line of the Prophecy of Seven: And foes bear arms to the Doors of Death. It took the combined effort of both Greek and Roman demigods (who are usually sworn enemies) to close the mortal side of the Doors. A team consisting of demigods (Percy Jackson and Annabeth Chase), Titan (Iapetus), and giant (Damasen) worked together to close the Doors from Tartarus, a notable feat considering that the three sides normally oppose each other.
While on their quest to free Thanatos, Frank Zhang, Percy Jackson, and Hazel Levesque learn that Gaea has taken control of the Doors of Death, allowing any deceased soul or monster in her cause to walk the earth once more. Upon releasing Thanatos in Alaska, the god reveals that he is unable to close the Doors while they are under Gaia's power. He explains that the demigods will have to go on a quest to the original Rome, and one of them must be able to read signs that lead them there.
Following the Mark of Athena beneath Rome, Annabeth survives a number of challenges single-handedly and proves herself Athena’s strongest and most worthy child. She finds the stolen Athena Parthenos statue in Arachne's lair, located above a pit to Tartarus. She manages to trick the weaver into trapping herself in a woven prison, and when the Argo II arrives to procure the statue, Arachne falls into Tartarus. She drags Annabeth with her, but Percy follows them as he does not wish to lose Annabeth again. Before falling into Tartarus, Percy makes Nico di Angelo promise to lead the Argo II to the House of Hades in Epirus, where the mortal side of the Doors of Death are located.
Percy and Annabeth, stuck inside Tartarus, journey towards the Doors as their only hope of getting out alive. First, they drink from the River Phlegethon and are almost attacked by Arachne. Along the way, they encounter many dangers, including the return of Kelli, an empousa killed by Annabeth in The Battle of the Labyrinth. This fight is made more difficult as Annabeth has lost the dagger Luke Castellan gave to her. However, the pair survive with the aid of Bob, formerly the Titan Iapetus, whom Percy dumped into the River Lethe, making him lose his memory.
Bob helps them until they find the arai, evil spirits who cannot be killed without a curse falling on the one who killed them. After Annabeth loses both her sight and her ability to find Percy, believing he has abandoned her after a curse made by Calypso falls upon her, Percy kills many arai and is near dead. Bob, however, decides to keep helping them even though he knows Percy betrayed him.
He carries Percy and guides Annabeth to the home of Damasen, a friendly giant cursed to remain in Tartarus for eternity. Damasen is impressed by Annabeth and agrees to heal Percy. Annabeth tries to persuade him to come with them and choose his own destiny, but Damasen maintains it is impossible. Annabeth, Percy and Bob leave without him.
Bob leads the demigods to Akhlys, goddess of misery, who shrouds them in a substance known as Death Mist, which will supposedly hide them from the monsters trying to hunt them down and kill them. Akhlys attempts to kill Percy, but he stops her with the sole use of his powers, choking Akhlys with her own poison before Annabeth stops him.
Unfortunately, Nyx finds them next, and wishes to kill them, following the common trend. Annabeth tricks her and her children with a tourist-related ploy, and she and Percy escape into the Mansion of Night. Somehow, Percy manages to jump several hundred yards over the River Acheron. They then reunite with Bob, who left them with Akhlys beforehand. They finally reach the Doors of Death together. Annabeth and Percy are preparing to destroy the chains that bind them when Tartarus himself appears and thwarts their plans.
They are both about to be killed, when Damasen turns up riding the drakon he was forced to fight before - he took Annabeth’s words to heart and found a new fate. He engages Tartarus in battle, and Percy argues with Annabeth, saying she should escape while he holds the Doors closed for her. She refuses, and Bob steps in. To Percy’s pain, he holds the Doors while Percy and Annabeth escape.
On the other side, Hazel Levesque and Leo Valdez have just defeated the sorceress Pasiphae and are trying to fight the giant Clytius, bane of Hecate, when Annabeth and Percy appear from the Doors, unconscious. They manage to destroy the chains holding the Doors grounded on their side and defear Clytius with the help of Hecate, Jason Grace, Piper McLean, Frank Zhang and Nico di Angelo. Together, the eight demigods escape.