The game takes place in Manhattan, New York City ten years after the events of Parasite Eve II. The player takes on the role of Aya Brea, and must fight against mysterious "Twisted" creatures threatening the city.

The game takes place in Manhattan, New York City ten years after the events of Parasite Eve II. The player takes on the role of Aya Brea, and must fight against mysterious "Twisted" creatures threatening the city.