Van Helsing/Best scene/Hugh Jackman/Kate Beckinsale/Anna Valerious/Will Kemp/Velkan/Tom Fisher

In 1887, Transylvania, Dr. Victor Frankenstein, with help from his assistant Igor and Count Dracula, successfully creates a monster. Dracula, a vampire, kills Frankenstein to use the creature for his own purposes. As an angry mob storms Castle Frankenstein, the monster flees to a windmill with his dead creator. The mob burn down the windmill, apparently destroying the monster.

One year later, monster hunter Van Helsing kills Mr. Hyde after a brawl in Notre-Dame de Paris. Van Helsing suffers from amnesia, slaying evil on behalf of the Vatican City, hoping that he will earn redemption for forgotten sins. He is tasked by Cardinal Jinette to go to Transylvania and destroy Dracula. He must also protect the last members of an ancient Romanian family, the Valerious, whose ancestor vowed that his descendants would kill Dracula, or fall into Purgatory. He receives a torn parchment, reading "In the name of God, open this door" in Latin.

Van Helsing travels to Transylvania, accompanied by Carl, an eccentric friar and inventor. Anna and Velkan Valerious attempt to kill a werewolf controlled by Dracula, but both it and Velkan fall into a river. Van Helsing and Carl arrive in a village, where they and Anna are attacked by Dracula’s three brides – Verona, Marishka, and Aleera. Van Helsing slays Marishka. Anna agrees to work with Van Helsing, but encounters Velkan, now cursed to become a werewolf during a full moon.

The two follow Velkan to Castle Frankenstein, now used by Dracula in an attempt to duplicate Dr. Frankenstein’s experiments to give life to his undead children, using Velkan as a conduit. While Anna tries to rescue Velkan, who succumbs to his curse, Van Helsing confronts Dracula, who expresses familiarity with Van Helsing, addressing him as “Gabriel” and offering to return his memories to him. Van Helsing and Anna flee the castle, Dracula discovering that his experiment has failed. Carl witnesses a painting come to life, depicting two knights respectively transforming into a vampire and a werewolf.

Van Helsing and Anna reach a deep cave below the destroyed windmill, where they meet Frankenstein’s monster, who is the true key to fulfilling Dracula’s plans. Van Helsing opts to shelter the monster in the Vatican. Just outside Budapest, the group are ambushed by the brides and Velkan. Verona and Velkan are both killed, but not before the latter bites Van Helsing, cursing him to become a werewolf. Anna is kidnapped by Aleera, who arranges with Van Helsing to trade her for the monster. Van Helsing locks the monster within a crypt, but he is captured by Dracula’s undead horde. Van Helsing and Carl save Anna, using a solar-based bomb created by Carl to destroy the vampires.

Returning to the Valerious family's castle, Carl explains that Dracula is, in fact, the son of Anna’s ancestor, imprisoned within an icy fortress, hidden behind a large walled map of Transylvania. Using the torn parchment, Van Helsing opens the door, finding Dracula’s fortress. The captured monster informs Van Helsing that Dracula possesses a cure for lycanthropy; Carl realizes that only a werewolf can kill Dracula. Capturing Igor, Van Helsing sends him, Anna, and Carl to retrieve the cure, while he frees the monster. As he does so, the monster is struck by lighting twice, bringing Dracula’s children to life. Dracula, spotting Van Helsing, transforms into a demonic form, fighting Van Helsing in werewolf form. Aleera and Igor are both killed as Anna and Carl retrieve the cure. Following a fierce skirmish, Dracula then reveals to Van Helsing he is in fact the archangel Gabriel and it was him who murdered Dracula. Dracula offers to restore all of Van Helsing's memories but he declines stating that some things are better left forgotten. Van Helsing then bites Dracula’s throat, killing him and his children. Van Helsing then kills Anna, but not before she delivers the cure.

Van Helsing and Carl host a funeral for Anna overlooking the sea, where the monster departs by boat. Van Helsing witnesses Anna’s spirit reuniting with her family in Heaven, freed of their vow. Van Helsing and Carl ride off on their next adventure.