When Isaac Clarke, an ordinary engineer, sets out to fix the USG Ishimura, a massive Planet Cracker-class ship, he finds that something has gone terribly wrong. Nicole, Isaac's cherished partner, is missing somewhere on board, and the ship's crew has been massacred. In an attempt to locate Nicole, Isaac, now alone and equipped only with his engineering knowledge and tools, races to solve the terrifying mystery of what transpired aboard the Ishimura. Isaac must fight for his life while surrounded by dangerous beings known as Necromorphs, not only against the ship's growing horrors but also against his own deteriorating mental state.