Gabriel Van Helsing, played by Hugh Jackman, receives a rather unwelcome command from the Vatican to track down and eliminate the notorious Count Vladislaus Dracula, portrayed by Richard Roxburgh. Fed up with being labeled a murderer for his actions against monstrous foes, Van Helsing longs for the restoration of his lost memories, taken due to his past transgressions. Cardinal Jinette (Alun Armstrong) emphasizes the significance of this mission; 450 years ago, a Transylvanian knight named Valerius the Elder made a sacred vow to God — that his lineage would not rest nor enter heaven until Dracula was defeated. With only two descendants remaining, Princess Anna, played by Kate Beckinsale, and Prince Velkan, brought to life by Will Kemp, the Valerius family's deadline looms as their souls hang in the balance.
Armed to the teeth with an assortment of weapons, including garlic, holy water, a silver stake, a crucifix, and an automatic crossbow, along with his comical sidekick, Friar Carl (David Wenham), Van Helsing makes his way to the dangerous land of Transylvania. Upon his arrival, the reception is anything but warm, as the local villagers resent outsiders. Tensions rise when three fierce harpies reveal themselves — Dracula's brides: Aleera (Elena Anaya), Marishka (Josie Maran), and Verona (Silvia Colloca). After several nail-biting encounters, Van Helsing kills Marishka, only to earn the ire of the villagers who claim that the vampires were relatively harmless, only taking a few lives a month. Consequently, they fear that her death will provoke the vampires into a killing spree.
As Van Helsing earns Princess Anna's gratitude for saving her life, she introduces him to her family's ancestral home, where she expresses her urge to confront the vampires at once. However, he opts to protect her instead, using a knockout spray to ensure she doesn’t rush into danger. When Anna awakens, she discovers that her brother, Velkan, who was believed dead, has become a werewolf after a tragic encounter with Dracula’s creature. A daring hunt begins as they seek a cure for Velkan, leading them to Castle Frankenstein, where an alarming experiment is underway — Dracula attempts to siphon Velkan's life force to animate a horde of vampire offspring who start to hatch before their eyes.
In a chaotic escape filled with fear, betrayal, and sacrifice, Van Helsing battles through various threats, including the fierce brides of Dracula and the tragic fate of Velkan as he dies in Anna’s arms. The stakes rise even higher when Van Helsing gets bitten by Velkan, resulting in a looming transformation into a werewolf. Despite this, the trio devises a desperate plan involving a masquerade ball to trade the Frankenstein monster for Anna. However, unexpected consequences unfold, and before they can reclaim her, Dracula vanishes, further complicating their mission.
Determined, Van Helsing, Anna, and Carl uncover the connection between Dracula and their family's past. Realizing they can access Dracula's icy fortress, they uncover the truth surrounding Van Helsing’s destiny intertwined with Dracula’s curse. As the clock approaches midnight, the tension escalates; Van Helsing transforms into a werewolf at the critical moment when the plan is set in motion to finally confront Dracula. With the antidote to his werewolf curse in hand, Anna joins the battle against Dracula, who reveals a shocking truth about Van Helsing's past.
As their final confrontation brews, Van Helsing struggles with his fate, compelled to face his demon while navigating love, loss, and the relentless pursuit of vengeance. In a touching conclusion, Anna’s sacrifice and Van Helsing's redemption result in a bittersweet farewell as he witnesses her spirit ascend, leaving him and Carl to forge their new path, riding into the sunset with a heavy heart but renewed purpose.
