In 1127 A.D., a group of English crusader knights capture a gem from ancient Egypt and bury it with them in death. In present day London, a construction crew discover the knights' tomb and a mysterious man is authorized to investigate the uncovered findings within the site. In a flashback, the heiroglyphics on a circular murial, which date back to the New Kingdom era, tell the story of Princess Ahmanet is first in line to succeed her father Pharaoh Menehptre, only to be stripped of her birthright when his second wife gives birth to a son. Determined to claim the throne for herself, Ahmanet sells her soul to the god Set, who gives her a special dagger to transfer his spirit into a corporeal form. After murdering her family, Ahmanet attempts to sacrifice her lover to give Set physical form, but her father's priests slay him and mummify Ahmanet, sentencing her to be buried alive for eternity with a sarcophagus.
In present day Iraq, soldier-of-fortune Nick Morton and his partner Chris Vail accidentally discover the tomb of Ahmanet after staging an airstrike on an insurgent stronghold. Jenny Halsey, an archeologist and former lover of Nick's, 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. In-flight, Vail becomes possessed by Ahmanet's power due to being bitten by a camel spider while inside the tomb. After attempting to open the sarcophagus, he kills Greenway and attacks the group before Nick shoots him dead. A huge wave 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 herself 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. At the last second, unknown soldiers appear and subdue her. Their leader, Dr. Henry Jekyll, explains that Jenny is an agent of Prodigium, a secret society dedicated to hunting supernatural threats whose base is under the Natural History Museum of London, and contains such objects as the hand of the Gill-man and a vampire's fanged skull. 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 for good.
Meanwhile, Ahmanet takes control of a Prodigium technician and frees herself from captivity, wreaking havoc, death, and destruction in the process. Jekyll succumbs to his own dark impulses and transforms into Edward Hyde, his murderous and psychotic alternative personality, nearly killing Nick before Nick manages to stop Hyde with the serum Jekyll uses to suppress himself. Nick and Jenny then escape 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.
Guided by Vail, Nick and Jenny flee into the subway tunnels under London, 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 stab 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 suck the life out of Ahmanet, turning her back into a shriveled mummy.
Nick uses Set's powers to resurrect Jenny, saying goodbye before becoming overwhelmed by Set's power and disappearing. Soon, Jenny links up with Dr. Jekyll and they discuss if Nick, now fused with Set, is good or evil and whose side he's on as Ahmanet's corpse is lowered into a locked pool of mercury within the Prodigium base for safekeeping. It is also revealed that Nick has resurrected Vail, who questions as to what they will do now, to which Nick responds, "Where's your sense of adventure?" The two ride off in the desert as a sandstorm trails behind them, with Jekyll telling Jenny that as long as a part of Nick's humanity remains, he will continue to search for a way to become human again.
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