Parasite Eve: The 3rd Birthday is set in modern-day New York City and follows the story of Aya Brea, a 25-year-old counter-terrorism agent who finds herself in the midst of a mysterious biological disaster. The game takes place on December 24, 2000, and revolves around a phenomenon known as the "Rebirth," where people are suddenly and inexplicably transformed into monstrous creatures. As Aya navigates through the chaos, she discovers that the events are linked to an ancient being known as Parasite Eve, which has the power to manipulate and control human bodies.