In the role of Lieutenant Ellen Ripley, the player experiences a story loosely derived from the first three films of the Alien franchise. Aside from occasional CGI cut scenes, the plot is told through text-based mission briefings that guide the player through an expanded, action-oriented story, drawing upon the settings and characters of the then-trilogy rather than through the specific plots of the films themselves.

The game begins in essentially the same manner as Aliens, as Ripley—here a marine herself—travels to LV426 to restore contact with the colony there. The other marines are wiped out, so Ripley must then travel through the infested colony and prison facility, and finally the crashed alien ship itself, to destroy the aliens and escape.