Isaac Clarke is a normal technician on a mission to maintain the USG Ishimura, a gigantic mining ship, only to find out that something terrible has happened there. The entire ship's crew has been massacred and Isaac's beloved partner Nicole is lost on board.
Now Isaac is on his own and must rely on his tools and skills to find Nicole. Slowly it becomes clear what horror has taken place on board the Ishimura. Amid the enemy nekromorphs, Isaac fights not only against the horrors on board, but also against his own dwindling wit.