In ancient Akkad in the year 2231 BC, the Akkadians are stuck with famine and plague, as well as a war with the Gutian people. The Akkadian King has fallen into madness, taking refuge in his great temple and executing Gutian prisoners as blood sacrifices. As the Gutians assault the temple, a solar eclipse occurs and unknown creatures appear, slaughtering both the Akkadian and Gutian armies.

Two survivors, Akkadian general Balathu and Gutian soldier Kurum, flee into the temple catacombs to escape the creatures. However, they are quickly overwhelmed and presumably killed. In 2003, USAF Lt. Colonel Eric King arrives in Iraq in the midst of the Iraq War. He briefs a team led by US Marines 1st Lt. Jason Kolcheck and Sergeant Nick Kay that they will be raiding storage detected by satellite that may be holding weapons of mass destruction.

The team also includes his estranged wife, CIA officer Rachel King. Meanwhile, an Iraqi soldier, Lt. Salim Othman, tries to deliver a present to his son but is forced by his commanding officer to intercept Eric's team. Salim's squad ambushes the team shortly after they land, but the fighting causes a cave-in that causes everybody to fall into the ancient Akkadian temple buried underground. Down inside the temple, both sides are assaulted by giant, bat-like creatures that they dub vampires. They also find the remains of a British archeological expedition led by Randolph Hodgson, who discovered the temple in 1946 but were killed by the vampires.

They also find out that the bodies of slain humans can also be reanimated as vampires. As the vampires continue to attack them, Salim reluctantly teams up with the Americans and they flee deeper into the ruins where they find the remains of a massive alien spaceship. By following Hodgson's path, the team learns that the vampires were originally a space-faring alien race that was afflicted by a parasitic infection. When they crashed to Earth, the infected aliens mutated and turned into feral monsters.

Trapped underground and vulnerable to sunlight, the monsters went into a state of hibernation for thousands of years, only occasionally venturing to the surface to feed. The team then finds a chamber holding thousands of hibernating vampires. Unwilling to risk them being unleashed on the surface, the team decides to plant explosives and destroy the entire chamber. They then flee and manage a find a way back to the surface, but another solar eclipse occurs. The surviving vampires then attack the team until the solar eclipse ends and a rescue team arrives to extract any survivors.

Depending on how well the team worked together, either all, few, or none of them survive the events of the game. Afterward, the American government seizes the ruins and begins studying the vampires while debriefing the surviving team members. As the credits roll, it is clearly stated that the government will cover up the entire incident.