Apart from the first one that Isaac finds on a workbench, all of Isaac's weaponry and items are found via schematics that are scattered across the ship. Isaac isn't the typical hero that you'd find in most sci-fi games he doesn't walk into the Ishimura packing a firearm or grenades, nor does he have specialized training. It's up to Isaac to wander the halls, search for any friends or survivors that are still alive, and fix as many problems as he can until he can find a way to escape the ship, which can take you 12 or more hours to complete. Even worse, the ship and its systems have started to be corrupted or are failing thanks to the Necromorphic infestation. The crew is attacked by nightmarish creatures known as Necromorphs, who kill most of Isaac's team and separate him from the surviving members. Their craft is destroyed, leaving them stranded on the Ishimura. Unfortunately for Isaac and his crew, shortly after they arrive on board the crippled vessel, all hell breaks loose.

Outside of fixing the communications issues, Isaac has a number of reasons for arriving on the Ishimura - he has a number of friends that are stationed on the ship, including someone very special to him that sends an urgent holovid with a few cryptic messages before she disappears. Players step into the boots of Isaac Clarke, a systems engineer that's part of the dispatched maintenance crew.

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