The game takes place just after the events of Alien³, involving a search and rescue team investigating the U.S.S. Sulaco (which has been abandoned and left floating in space), searching for Ellen Ripley, Corporal Dwayne Hicks, Private William Hudson, Private Jenette Vasquez, and the rest of the missing United States Colonial Marines. Other key areas include LV-426 and the Derelict alien shipwreck from the first Alien movie, as well as unnamed futuristic cities. The game's plot is being penned by Battlestar Galactica writers Bradley Thompson and David Weddle.

The player controls four colonial marines, each with their own unique personality. Each marine is represented by a different class; one marine, for instance, mans the M56 Smart Gun as Pvt. Vasquez did in Aliens; the other primary weapons include the M240 flamethrower and the M41A pulse rifle. Each marine carries four weapons: their primary weapon, which they are defined by, their secondary weapon, grenades, and a sidearm. The player may brandish the sidearm while using the motion tracker. The player controls one marine at a time, and issues orders to the others using context-sensitive commands; the player may control any marine at any given time. The game will feature no HUD whatsoever.

Xenomorphs will seldom perform a frontal attack, choosing to use the ducts and flanking maneuvers, forcing the player to use tactical combat as opposed to typical first-person shooter "run and gun" tactics. At certain points during the game, the player will be required to bunker in a location and prepare for a xenomorph onslaught, using tactical positioning and turrets to ward off an attack.

The game will use quicktime events during cutscenes to dramatically illustrate the power and intensity of one-on-one xenomorph encounters. However, the conclusion of a given event is not scripted; a xenomorph may choose to attack or flee when confronted by more than one marine. Quicktime gameplay is also used when a facehugger latches onto a player, who must kill the creature before they are effectively incapacitated and "killed" by it.

Xenomorphs themselves will have subtle classes. The following classes are confirmed:

• Facehugger: the eight legged parasite that attaches itself to the victims face and lays an embryo within the living host, and dying shortly afterwards
• Warrior: typical of the attacking xenomorphs in Aliens
• Scout: a faster, more stealthy xenomorph who spies on Marine activity
• Drone: a new servant xenomorph who carries and positions eggs
• Queen: a game boss