The newest incarnation of the game takes place after Ripley and the surviving Colonial Marines leave planet LV426. A mopup operation headed by the colonial marines returns to the planet to finish off the Alien population that ravaged their troops years before. In the game the players take control of one of the best weapons in the Colonial Marine arsenal the M41A 10mm Pulse Rifle, over and under, with a 30mm grenade launcher

Years after Alien3, two Colonial Marine squadrons are sent back to the destroyed Hadley's Hope on LV-426 to exterminate the Alien presence. Upon arrival at the colony, the Marines encounter not only the Aliens, but also a malfunctioning defense system. They eventually manage to destroy the system's power generators and shut the system down. The Marines continue their mission, fighting their way through the Aliens, and, eventually, are confronted by Weyland-Yutani synthetics that have been reprogrammed to capture Alien specimens and re-purpose them as biological weapons. After fighting their way through Aliens and sythetics, the Marines encounter a synthetic in a Power Loader armed with a buzz saw.

After dispatching the synthetic, the Marines continue their mission and eventually discover a winged Alien. Eventually, the marines "slay" the "dragon" and make their way to the heart of the colony. There, they find the Hive's Queen waiting for them. While the players distract the Queen, their squad mates arm a nuclear explosive device to destroy the colony. Eventually, the players defeat the Queen and begin to evacuate. As they are riding an elevator up to the surface, the Queen, not quite dead yet, pursues them and tries to kill them. The players manage to hold her off and the Marines escape, leaving the Queen trapped in the explosion. However, several Aliens infiltrate the players' dropship, leaving the players' fate unknown.