The film begins with a man on the streets looking for a prostitute. When he finds one, the man pulls out a razor and threatens the woman. Derek Bliss (Jon Bon Jovi) then comes up and points an odd-looking gun at his left temple. After the man backs away, the prostitute thanks Derek and asks if she can do anything for him. He turns the gun on her and shoots her with three stakes, and it is revealed that the prostitute was a vampire. Derek drags her to an abandoned car lot and watches her catch fire in the sunlight while filming it on camera.
When he gets back to his hotel room, the Van Helsing Group leader calls him and informs him that he has a new job. He goes down to Mexico to a convent where a group of vampire-hunting priests are staying. He has a strange vision, and one of the priests conclude that the vampires may be linking up with him.
That night, Una (Arly Jover), a vampire princess, and her fledglings attack and feed upon a human man. The next day, Derek goes looking for people on a list he has been given. Unfortunately, most of them are dead or crazy, and the last living ones are killed. Derek goes to a coffee shop and asks for a man named Jesse. He tells Derek to wait while he finishes up something. Derek then meets a young woman named Zoey (Natasha Gregson Wagner), and he grows suspicious when she asks him if he works in the "undead" business. He leaves to go to the bathroom, and finds out that Zoey is a vampire by using a special lens, lamenting the fact as he thinks she's cute. In the split second it takes him to throw a paper towel in the trash, Una comes in, slashes the throat of every customer, and kidnaps Jesse.
When Derek comes out and sees that Zoey has also fled, he concludes that she must have done it. The next day, he pulls over when sees her on the side of the road. They argue; Zoey tells him about special pills she takes to fight off her vampire side. She has a vision of a monastery, and Derek realizes that it is the one where he just left. They drive back and find all but one priest slaughtered. Father Rodrigo (Cristián de la Fuente) tells them of the Berziers Cross which is being sought by Una as it can be used to perform a ritual that will enabled vampires to walk in daylight and be invulnerable, and shows them something a fellow priest was working on in his spare time: a huge van complete with all the necessary vampire-slaying tools. Derek hears a noise in the trees, and finds a teenager that he had met before. His name is Sancho (Diego Luna), and he has a permission slip from his mother, stating he can go on the vampire hunt with Derek.
The group meet up with another hunter, Ray Collins (Darius McCrary) from Memphis, and go after Una. Una seduces Ray and convinces him to leave Zoey's pills where she can get them. When they reach the village where the vampires are hiding out, they are welcomed because they want the vampires killed. Una, now able to walk in daylight, goes out and kidnaps Zoey. Derek aims the gun at Sancho and says he must have given the pills to Una. However, a villager realizes that Ray did it, and shoots him before Derek shoots Sancho. Derek and the gang go after Zoey to rescue her, at the cost of leaving Rodrigo to properly perform the ritual. They go back to a clinic, where Zoey's vampire blood is exchanged for human blood. Derek knows how to save Rodrigo; the vampire blood is pumped into his body.
The team goes after Rodrigo and find out that he was not a real priest. Una is not daunted, and she responds by lighting a fire beneath his feet. Derek saves Rodrigo, and goes after Una. They almost kill her, but she escapes when the cord which was dragging her into the sunlight snaps. She catches Derek, but Derek then grabs what is left of the cord. Before they reach the sunlight, Derek shoots her head off with a shotgun and sends it flying into the sun, where it catches fire. Her body turns into stone with a black beating heart in the chest. Derek drives a stake into the heart. Sancho and Rodrigo decide to stay in the village, and Derek and Zoey drive away in the sunset.Jon Bon Jovi as Derek Bliss
Cristián de la Fuente as Father Rodrigo
Natasha Gregson Wagner as Zoey
Arly Jover as Una
Darius McCrary as Ray Collins
Diego Luna as Sancho