- "Survival of the fiercest."
- ―Aliens versus Predator: Extinction tagline
The game is the fourth in the Alien vs. Predator franchise, although it bears no relation to the other titles beyond its general concept. The player can choose to play as Alien, Predator or Colonial Marine forces.
Humans arrive on a newly colonized world known as LV-742 and discover an Alien (Xenomorph) colony, unaware that a hunting party of Predators are also present on the planet, stalking their favoured species, the Xenomorphs. Minor battles between the humans and the Predators soon escalate into an all-out war. Meanwhile, the colony of Aliens escape and attempt to overwhelm both factions.
In Aliens Versus Predator: Extinction, the Weyland-Yutani Corporation sets up a colony on planet LV-742 after discovering a battle between a clan of Predators and an Alien hive. The game allows the player to control three different species: Aliens, Predators and Colonial Marines—another organization originally featured in the Alien film series and subsequently seen throughout the AvPseries. Playing in the Predator Campaign, players control a clan that must win the respect of the Ancients, introduced as the rulers of the Predator race, and in order to win their approval you must hunt a legendary beast called the Gro'Tye, and after that you must hunt the Alien hive in several missions in the campaign. In the sixth mission you must assassinate another Predator who allowed himself to be captured instead of fighting to the death for two reasons.
- It is a dishonor to let yourself be captured
- The humans must not discover the secrets of Predator technology
Even if you do succeed in killing the Predator, you are still in danger as a Weylend-Yutani scientist creates the unimaginable, an Alien queen based on Predator DNA. This is a serious crime and you must kill the PredQueen at all costs, along with her hive. Your clan is not alone on this hunt as one of the Ancients is joining you as he has a nuke strong enough to wipe out a hive in ten seconds. Players must be very careful in this mission as they face every single alien breed in the game and hundreds of PredAliens. After you kill the PredQueen, which is not easy, you must have a member of the clan take it to your shrine. After you kill every Alien in the hive, your Ancient, who you must keep alive because otherwise will fail the mission, will nuke the hive. Once the Ancient detonates the nuke your screen turns white and the campaign is complete.
In the Alien Campaign, you start off with a Drone and batch of eggs and you are caved in an underground system for hundreds of years, possibly from a previous war. The Weyland-Yutani colonists drill open your cave and you are now given access to bring hosts back to your eggs. One of the eggs contains a Praetorian, which you must use to breed a Queen in order to continue populating the hive. Later, a few Marines arrive to wipe out your hive, but you should have around thirty aliens from hosting the colonists and Oswocs outside your hive entrance. Once the hive is large enough, you must send a swarm of aliens to wipe out the Marine base in the North.
A few years later, which is the setting of the second mission, a Marine demolition charge has destroyed your underground hive and wiped out its population. But the battle is not over yet, as your Queen and a few other Aliens have survived the attack. You must now put your Queen into a secure area guarded by the other Aliens so she can start laying her eggs. Discovering that your hive is still breeding, hordes of Marines are dispatched to attempt to wipe out your hive. Now you are only left with one option, to get a Queen into the nearby Weyland-Yutani facility and onto a dropship to get your species off LV-742.
If you succeed in this, then your Queen will be taken to a jungle environment. But the dropship was shot down and now you have crashed. You are now in the same jungle as your kinds' greatest rivals and arch enemies, the Predators. Now that your Queen is aware of the Predator's presence, she now hungers to use them as hosts to breed stronger Aliens.
Soon the Predator clan sends a Stalker, Brawler, Spear Master, Hunter and a Disc Master. In order to fight the hunters, the Queen must start laying eggs so the Predators will get overwhelmed and you will have PredAliens in the hive. When the hive is full of Warriors and PredAliens, you will have to kill the leader of the Predator clan, which is a Vanguard. Either keep your Queen far away from the clan in order to continue laying eggs or send in your Queen and have a Praetorian near a batch of hosts. After you succeed in eliminating the clan, your eggs have been stolen by the Weyland-Yutani Corporation for tests on your species. After the tests end, Predators will attack the labs and this will cause the security systems to go offline and allowing one of your Warriors to escape and free the other members of the hive and breed a Queen.
- Commtech: AURORA Control which is an orbital laser assassination system.
- Medic: Counterxenology which heals acid wounds, cystic tumours, and more.
- Synthetic: Combat Modifications which grant a Synthetic more armor, better weaponry, and allows an incapacitated Synthetic to be brought restored by a Commtech.
- Infantry: Heavy Assault Kit in which infantry units gain a M41A Pulse Rifle and M4X Armor.
- Flamethrower: Cobalt Thermoge
- Smart-gunner: M57D "Dirty" Smartgun
- SADAR: M83AM SADAR AMAG, upgrades this unit to be armed with the
- Sniper: The Sledgehammer
- Hunter: Omni-viewer
- Brawler: The Glory Strike
- Spear Master: Plasma Glaive
- Stalker: Bleeder Spears
- Egg/Praetorian Egg: Adaptive Hyperfertility
- Queen: War Empress
In AVP: Extinction, the game is divided into three campaigns of seven missions for each species. Each race has a unique method of gathering resources; humans must use a CommTech (a lightly armed Marine technician) to repair Atmosphere processors in order to summon dropships that deliver troops, while the Predators need to remove skulls from dead enemies to gain Honour Points, which are used to orbitally drop Predators from space. Aliens gain Infestation Points by immobilizing or killing prey.
There are several types of damage in this game (such as fire, energy, kinetic, or raw armor-piercing damage), and status effects, such as radiation poisoning and bleeding. Many units have weakness or resistance to one or more damage types, for instance PredAliens take less fire damage than normal.
Each unit in the game has varying strengths and weaknesses; for instance, the Predator Spear Master is excellent at dealing with large crowds of smaller opponents, such as Runners or Warriors due to its knockback abilities, but larger enemies such as the PredAlien cannot be knocked over and cannot be quickly defeated. Meanwhile, the Predator Vanguard is excellent at quickly killing difficult opponents, even a Queen, but its long windup time for its weapon makes it vulnerable to swarms of smaller enemies. Each unit in the game has an upgrade, which increases its power in some way; Warrior Aliens gain the 'Onslaught Genome' which allows them to deal raw damage and continue fighting even if they lose limbs, while the Ravager gains 'Colossal Resilience' which makes it vastly more difficult to destroy. It should be noted that while in most media the Predators can carry many types of weapons, in AVP: Extinction, each Predator unit only uses one type of weapon in combat.
Aside from the single-player campaign, there is a guide to the various units, including background information on their equipment and training. However, there is no multiplayer or skirmish mode.