In 1897 England, the ominous schooner Demeter nears its port, but its fate is grim—the crew lies lifeless, and the captain is tied to the wheel, marking the arrival of Dracula. Fast forward to 2000 London, where Matthew Van Helsing (Christopher Plummer), an elderly antiquities collector, discusses the acquisition of a medieval crossbow with his protégé, Simon Sheppard (Jonny Lee Miller). Matthew seeks to enrich his personal collection at the Carfax Museum, which also conceals a fortified vault shrouded in mystery.
Among the public exhibits, the vault is safeguarded by numerous vampire skulls and crosses, piquing the interest of a colleague, Solina (Jennifer Esposito), who has plotted a heist to infiltrate the vault. As Matthew prepares to leave for the day, Solina and her crew—comprising Marcus, Trick, Nightshade, Dax, Charlie, and J.T.—successfully crack the security codes. They venture into the vault, only to discover a coffin amidst the artifacts, suggesting hidden treasure. As they attempt to lift its lid, tragedy strikes when Eddie and Dax fall victim to sharp spikes, triggering an alarm in Matthew's office. In disbelief, Matthew arms himself with a silver bullet gun and rushes to the vault, discovering the coffin mysteriously missing, its excise facilitated by a tunnel blasted into the wall. "God help us all!" he gasps.
The next day, Simon arrives at the museum to find Matthew prepared for an undisclosed journey to New Orleans. Meanwhile, a young woman named Mary Heller (Justine Waddell) awakens from a haunting dream where a vampire attacks her—a nightmare that has plagued her since childhood, leading her to seek counsel from Father David (Nathan Fillion). Though he possesses knowledge of her troubled past, he remains silent, while her friend Lucy Westerman (Colleen Fitzpatrick) believes Mary simply needs romance amidst the Mardi Gras festivities.
Meanwhile, the thieves are airborne, transporting their stolen coffin. After some time, Nightshade inadvertently cuts himself, causing blood to seep into the coffin, which subsequently opens, revealing a body, leeches, and a crucifix adorned with a ruby. As Nightshade scavenges for more treasures, Dracula (Gerard Butler) awakens and methodically drains the gang of their life force. The chaos culminates in the plane crashing into a swamp outside New Orleans, leaving the pilot bound to his seat.
As news reporter Valerie Sharpe (Jeri Ryan) covers the disaster, Dracula emerges from the mire, escalating the horror by turning Valerie into his second vampiress after Solina. Matthew and Simon investigate the town hall, now filled with vampiric bodies from the crash site, and manage to destroy a few. Yet, Solina and Marcus evade capture. Matthew finally reveals to Simon the chilling truth: Stoker's Dracula is not fiction, and he himself is Abraham Van Helsing, cursed to live by the flow of Dracula's blood. He has kept Dracula's body since triumphing over him in 1897, with the ultimate goal of unraveling the secrets of his origin and finding a way to truly end him.
The duo visits Mary's house, unaware that Dracula is on the same path. At the local Virgin Megastore, Lucy misleads Dracula, and he subsequently seduces and transforms her into vampiress three. Once Simon meets Mary, he implores her to understand her father's legacy, and upon their departure from the store, Simon faces an ambush from Marcus. With a resolute warning, "Never ever fuck with an antiques dealer," Simon beheads him. Meanwhile, Van Helsing confronts Dracula, declaring, "You can't have her!" but the ancient vampire retaliates, extinguishing Van Helsing's life by hurling him into a mirror.
As Mary rushes home, she discovers a devastating scene: her father's lifeless body lies amidst the vampiric threats of Dracula and his newly turned followers. In a desperate escape, Mary finds sanctuary in Simon's arms. The pair seek refuge in a church and research Dracula's malevolent history, fathoming his aversion to anything holy. It isn’t long before Dracula surfaces, and a game of cat and mouse ensues, leading Mary into the cemetery. There, Dracula, revealing himself to be Judas Iscariot—the disciple infamous for betraying Christ—confesses, "I have walked the earth for centuries in search of a soul not bitten but born. Everything I am is yours, and all that you are is mine."
In a final confrontation, Simon takes action against the vampiresses, staked by him. Amidst the ensuing chaos, Mary must confront her fate and her lineage. Ultimately, the confrontation crescendos as Dracula, captured in a moment of vulnerability and ensnared, meets the dawn's light, igniting in flames. With her father's legacy on her shoulders, Mary resolves to safeguard Dracula's remains, vowing to prevent his resurrection at any cost.
