Isaac Clarke is an everyman engineer on a mission to repair a vast, sprawling starship, the USG Ishimura, only to discover something has gone horribly wrong. The ship's crew has been slaughtered and infected by some alien scourge...and Isaac’s beloved partner, Nicole, is lost somewhere on board.

Now Isaac is alone with only his tools and engineering skills as he attempts to uncover the nightmarish mystery of what happened aboard the Ishimura. Trapped with hostile creatures called “necromorphs”, Isaac faces a battle for survival, not only against the escalating terrors of the ship, but his own crumbling sanity.