Lara Croft arrives at the Temple of Osiris, in Egypt, hoping to be the first inside, but rival treasure hunter Carter Bell has beaten her to the entrance. They each seek the Staff of Osiris, but they discover more than they bargained for.
Upon entering the tomb, Carter removes the mythical Staff from its resting place and inadvertently triggers a trap, cursing them both and unleashing the evil god Set. But the Staff also awakens the gods Horus and Isis, the son and wife of Osiris. Now free from their ancient prison, they join forces with Lara and Carter in order to resurrect Osiris, the only god capable of removing the curse and returning Set to Duat, the Egyptian underworld.
Lara and her companions fight their way across the sands and through many ancient tombs, recovering the dissected fragments of Osiris' body in order to assemble him to take down Set. They face resurrected ancient soldiers, a Pharaoh and several Gods, until the only thing they have left to find is one final canopic jar, which is in the possession of Set.
Somehow, even with one fragment missing, Osiris is able to return to the world. He helps Lara, Carter, Isis and Horus to battle Set and his minions, and he pushes Set back into Duat. He removes the curse that was placed on Lara and Carter and returns to the underworld himself. Isis and Horus stay in the temple to guard the Staff of Osiris once more as Lara knows that one day, Set will return to the world to try again with his destruction, and she vows to be ready to fight him again.