The film begins in black and white, set in Transylvania, 1887. Doctor Victor Frankenstein brings to life the Frankenstein’s Monster but his triumph is cut short when an angry mob infiltrates the castle. Dr. Frankenstein has been aided in his experiments by his deformed assistant Igor, and Count Dracula. Dracula reveals that he helped Frankenstein so he could use the Monster for his own purposes, later revealed to be using the Monster to bring his undead children to life. Frankenstein refuses to help Dracula and tries to kill him, only to discover the Count is already dead. Dracula kills Frankenstein, but the Monster breaks free, knocks Dracula into a fireplace and escapes to a windmill with his “father’s” body. The mob pursues him and burns down the windmill. The Monster and Frankenstein fall into the ruins of the windmill and disappear. Dracula (who survived the fireplace) and his three brides, Verona, Marishka and Aleera, arrive at the remains, their plans seemingly lost.
The film then leaps forward one year and changes to color, introducing Van Helsing a monster hunter who works for the Knights of the Holy Order at Vatican City.
After unintentionally killing Mr. Hyde in Paris, Van Helsing returns to the Vatican where he is assigned his next mission by a priest. He is sent to Transylvania to help the last of the Valerius family, Anna, to destroy Dracula; otherwise many generations of the family will never go to Heaven. This is because one of Anna’s ancestors vowed that his family would never rest in peace until Dracula is dead. Anna’s brother, Velkan Valerious, actively searches for various monsters. He is bitten and turns into a werewolf.
Van Helsing takes Carl with him, an intelligent but bumbling friar who doesn’t really mind blaspheming (as he swears several times and later sleeps with a Transylvanian woman). The two arrive in a town, where they meet Anna, who is the last Velarius after her brother Velkan fell into a river whilst fighting a werewolf. The three brides attack the town, but Van Helsing kills Marishka by firing arrows covered in holy water at her. Anna reluctantly accepts Van Helsing’s help and takes him to her castle home. That night, a werewolf shows up. He is revealed to be Velkan, bitten by the previous wolf. Velkan retreats to Frankenstein Castle with Van Helsing and Anna in pursuit, the werewolf killing a creepy gravedigger in the process. Velkan is strapped into a special device by Dracula, in order for Velkan to act as a conductor for electricity to bring Dracula’s children to life. The process works briefly, but the children begin to die shortly after birth. Anna releases Velkan but he becomes a werewolf again. Van Helsing meets Dracula, who addresses him as “Gabriel”. Van Helsing tries to stab him with a stake and burn him with a holy cross, but neither harm him.
Van Helsing and Anna escape but fall into an underground cavern, discovering the Frankenstien Monster hiding from Dracula. Anna suggests killing the Monster, but Van Helsing decides to take him to Rome to protect him from Dracula. Picking up Carl, the group (Van Helsing, Anna, Carl and the Monster) head off in horse-drawn carriages. However, the remaining brides and the Velkan werewolf chase after them. The carriage falls down a ravine, the brides pursuing it but discovering it is a decoy with a box of stakes inside. The carriage hits the ground and explodes, catapulting the stakes in all directions, some of which impale Verona and kill her. The real carriage containing the group nearly gets away, but the werewolf appears and set the carriage on fire. Van Helsing fires his shotguns on the werewolf and kills him. Anna finds Velkan shortly before he dies; she also discovers Van Helsing was bitten in the process and will become a werewolf. Anna is then kidnapped by Aleera, who bargains with Anna for the Monster. Instead, Van Helsing knocks the Monster out and places him in a tomb to keep him from being stolen. Van Helsing and Carl sneak into Dracula’s summer palace where a ball is occurring. Van Helsing rescues Anna from being bitten, but discovers the Monster has been captured by the undead, who are then sent after Van Helsing and the others. The undead are destroyed by a weapon created by Carl that releases a bright exploding lightsource.
The trio returns to Anna’s castle and piece together that Dracula was killed in the 1400s, made a deal with the Devil and became a vampire; Dracula is actually the son of Anna’s ancestor; and the only way to kill Dracula is by using a werewolf. The group then discover the door to Dracula’s lair: a large map owned by Anna’s deceased father. A missing piece is in the possession of Van Helsing, who received it from the Vatican priest. The three travel through the door and find an icy fortress: Dracula’s lair.
Inside, Van Helsing sees the Monster, who explains that Dracula has a werewolf cure. Anna and Carl force a captured Igor to take them to the cure, but are attacked by Aleera. Carl heads off with the cure to find Van Helsing, who must kill Dracula and receive the cure before the final stroke of midnight, or he will permanently become a werewolf. Carl is pursued by Igor, who attacks him with a tazer-like weapon. Van Helsing manages to free the Monster but not before Dracula’s children are brought to life. Dracula attacks Van Helsing, transforming into a demonic winged vampire. The Monster falls off a tower and is propelled through the air on a wire, which collides with Igor, sending him plummeting down a ravine to his demise. The Monster distracts Aleera, allowing Anna to escape. However, this distraction lasts for only so long when Aleera confronts Anna. Anna stabs Aleera with a concealed stake, killing her. Van Helsing, transformed into a werewolf, fights Dracula until the full moon is blocked out by clouds. Dracula takes this opportunity to reveal that Van Helsing is the Left Hand of God, another name for Gabriel, and it was he who killed him in the 1400s. Dracula attempts to get Van Helsing to be his partner. Van Helsing refuses, returns to werewolf form when the moon comes out again, and kills Dracula by biting his neck. Dracula and his children all die. Anna rushes in with the cure, after receiving it from Carl, and races to save Van Helsing, but he attacks and kills her in werewolf form. However, she has managed to inject him with the cure. Restored to humanity, he holds her body in his arms.
Van Helsing and Carl cremate Anna’s body by the ocean shore, honoring Anna’s unfulfilled desire to see the ocean. Van Helsing briefly sees a vision of Anna and her family in Heaven, before he and Carl head off back to Rome. The Monster, having survived, rows off on a raft to an unknown future.
