Acting on a distress call by the mining ship USG Ishimura, engineer Isaac Clarke is dispatched to diagnose and fix its problems. Soon upon arriving, Isaac finds that the crew have been slaughtered and the ship is now filled with terrifying creatures known as Necromorphs.

Faced with limited supplies and weapons, Isaac must survive the horrors of this sinister spaceship as he attempts to escape, and perhaps put an end to the necromorphs.