Apparently the sole survivor of the mission to the USG Ishimura and the Aegis VII incident, CEC engineer Isaac Clarke is brought back to Titan Station in orbit around Saturn. Diagnosed with paranoid schizophrenia, Isaac is committed to an Earth Government-run asylum.
However, whatever was at Aegis VII seemed to follow Isaac to our solar system. As the game begins, Clarke is in a padded cell of the asylum. Then all hell breaks loose. Without his heavy-duty RIG suit, Isaac must rely on other means to get him through this latest horror.