When human forces discover the existence of the Vampire and Lycan clans, a war to eradicate both species commences. Selene, a vampire warrior, leads the battle against humankind. Twelve years later, Selene is freed from cryogenic suspension and encounters a young girl named Eve, revealed to be her and her lover Michael's daughter. Together with Eve and David, a fellow vampire, Selene fights against Antigen, a medical corporation conducting experiments on vampires and Lycans. Selene must save Eve and defeat the lycans, while seeking to find Michael and take back the world from humans and lycans.

Underworld: Blood Wars tells the story of Selene, a vampire death dealer, as she fights to protect the vampire race from the vicious Lycans. When she discovers that a new enemy has emerged, Selene must form an alliance with David and Thomas to stop a powerful and ancient foe. As the war between vampires and Lycans escalates, Selene faces betrayal, conspiracies, and a fight for her own survival.

Vampire Selene and half-werewolf Michael seek the truth about their races and the war between them, following the events of the previous movie.

Set centuries before the events of the first Underworld film, the movie follows the rise of the Lycans, a slave race of werewolves, and their conflict with the aristocratic vampires. As the vampires attempt to exterminate the Lycans, a forbidden love and a rebellion brew, leading to an epic battle for freedom.

Selene, a vampire warrior, is entrenched in a conflict between vampires and werewolves, while falling in love with Michael, a human who is sought by werewolves for unknown reasons. The war between the two species has been raging for centuries, with vampires employing Death Dealers to hunt and kill the remaining werewolves. Selene discovers that the Lycans have devised a new weapon that can kill vampires and uncovers a plot involving a hybrid creature that could change the balance of power. As Selene and Michael fight for their lives, they must navigate a web of betrayal and deception to uncover the truth and save themselves.