In 1127 A.D., several English crusader knights bury an Egyptian ruby within the tomb of one of their number. In present-day London, a construction crew discovers the tomb and a mysterious man is authorized to investigate the site.

In a flashback to the New Kingdom era, Princess Ahmanet is first in line to succeed her father Menehptre until his second wife gives birth to a son. Determined to claim the throne for herself, Ahmanet summons Set, who agrees to help her if she uses a dagger to transfer his spirit into a corporeal form. After killing her family, Ahmanet attempts to sacrifice her lover to Set but is captured by her father's priests and condemned to be mummified alive for eternity. Her sarcophagus is buried in Mesopotamia and submerged in a pool of mercury so that her monstrous form will not escape.

In present-day Iraq, Sergeant Nick Morton and Corporal Chris Vail, while on Long Range Reconnaissance for the U.S. Army, discover the tomb of Ahmanet after calling in an airstrike on an insurgent stronghold. Jenny Halsey, an archaeologist who had a one-night stand with Nick, arrives and investigates the tomb, correctly concluding that it is a prison. After extracting Ahmanet's sarcophagus from a pool of mercury, Nick's superior, Colonel Greenway, places the sarcophagus on a transport plane headed to England. During the flight, Vail becomes possessed by Ahmanet's power after being bitten by a camel spider while inside the tomb. After attempting to open the sarcophagus, he stabs Greenway and tries to attack the group, forcing Nick to kill him. A huge murder of crows then assault the plane, causing it to crash and kill everyone on board except for Jenny, who is parachuted off the plane by Nick.

Nick awakens a day later in a morgue in Oxford, and learns from Vail's ghost that he has been cursed by Ahmanet, who seeks to use him as a replacement vessel for Set. Ahmanet's mummy escapes from the sarcophagus and begins feeding on rescue workers to regenerate her decomposed body. Turning the workers into zombie minions, she lures Nick and Jenny into a trap, forcing the two to fight off the minions as they unsuccessfully try to escape. Ahmanet also recovers the blade of the Dagger of Set from a reliquary in a nearby church. At the last second, unknown soldiers appear and subdue Ahmanet. Their leader, Dr. Henry Jekyll, explains that Jenny is an agent of Prodigium, a secret society dedicated to hunting supernatural threats. He confirms that Nick was cursed when he unlocked Ahmanet's tomb and reveals his intention to complete her ritual and allow Set to possess Nick in order to destroy Set and end his evil forever.

Meanwhile, Ahmanet summons a spider to possess a Prodigium technician and frees herself from captivity, wreaking havoc, death, and destruction in the process. Jekyll is also seen to be succumbing to his own dark impulses and transforms into Edward Hyde, his murderous and psychotic alternate personality while Ahmanet wreaks havoc outside unknownst to them. And when Nick rebuffs Hyde's offer of an alliance between them, Hyde attacks him. Nick manages to stop him with the serum Jekyll uses to suppress his evil side. He and Jenny then escape from Prodigium while Ahmanet steals back the dagger, summons an army of deceased English crusaders to serve her, and creates a massive sandstorm that ravages London. The undead knights slaughter the Prodigium soldiers in the tomb, allowing Ahmanet to recover the ruby and set it in the dagger's pommel, granting her all she needs to free Set.

Guided by Vail, Nick and Jenny flee into the London Underground tunnels, but are attacked by Ahmanet's minions. Ahmanet captures Jenny and drowns her, hoping to break her hold over Nick. Nick puts up a fight, but gives up and lets himself embrace Ahmanet, using it as a ruse to steal the dagger and tries to destroy the ruby. However, he sees the lifeless Jenny and bets on stabbing himself. His body is possessed by Set, who proceeds to join Ahmanet to uphold his end of the bargain until he sees Jenny's dead body, at which point Nick regains control and uses Set's powers to overpower and suck the life out of Ahmanet, turning her back into a shriveled mummy. Nick harnesses Set's powers to resurrect Jenny, saying goodbye before becoming overwhelmed by Set's power and disappearing. Soon, Jenny regroups with Dr. Jekyll and they discuss if Nick, now fused with Set, will be good or evil. Ahmanet's corpse is lowered into a locked pool of mercury within the Prodigium base for safekeeping. Later on in the desert, Nick resurrects Vail, and the two set out on an adventure to find a cure.

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