It's 2000 London and antiques dealer Abraham Van Helsing (CHRISTOPHER PLUMMER) has an oldie but a goodie securely tucked away in his subterranean vault, or so he thinks. Unfortunately for him, one of his employees, Solina (JENNIFER ESPOSITO), has arranged an inside theft job that's to be carried out by outsider Marcus (OMAR EPPS) and his team of high-tech thieves including Trick (SEAN PATRICK THOMAS), Nightshade (DANNY MASTERSON), Eddie (LOCHLYN MUNRO) and Dax (TIG FONG).
When they eventually arrive in the inner sanctum of his vault, however, all they find is a booby-trapped and seemly impenetrably sealed coffin. Figuring it must be filled with something valuable to warrant such security surrounding it, the thieves remove the coffin and head off for the Caymans. Of course, Van Helsing knows that the coffin really contains Dracula who's been contained within it for the past century or so. As such, he sets out to retrieve the vampire, telling his assistant, Simon (JONNY LEE MILLER), to stay put and run the shop.
Meanwhile, in New Orleans, Mary (JUSTINE WADDELL) is a young record store employee who's been plagued by nightmares and bizarre dreams about Dracula ever since she was a kid. Her housemate, Lucy (VITAMIN C), thinks Mary just needs a man in her life, but Mary truly believes she's going crazy.
When the thieves' plane crashes not far away after the rejuvenated Dracula (GERARD BUTLER) has killed or turned the robbers into more vampires, however, Mary soon discovers the truth behind her dreams. With Van Helsing arriving to save her and capture Dracula, and Simon following him to figure out what's going on, it's only a matter of time before the vampire finds Mary. From that point on, Van Helsing and Simon do what they can to stop Dracula and the many new vampires, including local TV reporter Valerie Sharp (JERI RYAN), that he's created.