Percy Jackson and The Titan's Curse marks the return of demigod son of Poseidon, Percy Jackson, as he embarks on a mission to save his kidnapped friend Annabeth. The book opens with Percy, Thalia and Annabeth travelling to Westover Hall to help the half-bloods, Nico and Bianca. Artemis comes to their aid when Dr. Thorn springs a surprise attack on them. However, even though they survive they realize Annabeth has been kidnapped.

Percy then goes off seeking Artemis to join them for a council meeting at Olympus. They learn that Luke's army has imprisoned Artemis. Percy and his friends set out to free Artemis and Annabeth. Enroute, Percy is requested to help rescue Ophiotaurus, a cow-like being, who prophesied Olympus ruin. Percy also seeks the help of a Pegasus, Blackjack, to catch up with the others.

Percy Jackson and The Titan's Curse describes the fight that takes place during the rescue mission. Apollo lends them his help and provides them with the use of a freight train to get to Cloudcroft. They receive another gift from Pan, a giant boar, that takes them to Gila Claw. Later, Percy and his friends come in contact with a mortal, Rachel, who is gifted with the ability to see through the Mist.

During their journey, Bianca mistakenly awakens a Hephaestus prototype called Talos. Once they reach Mount Othrys, they find that Artemis has taken up Atlas burden of holding up the sky. How do they manage to take this burden away from Artemis? with Annabeth's life in danger, her father also comes to the groups aid.