In the early 20th century, Transylvanian vampire Count Dracula meets English lawyer R. M. Renfield. Renfield hopes to broker a deal for some land and after proving to be a useful assistant, he ends up becoming Dracula’s familiar, allowing him to be immortal and gaining super strength and speed when he consumes bugs.

Ninety years later, Renfield has grown weary and exhausted of bringing victims to Dracula as well as the latter’s abuse. They recently had a close call with some vampire hunters who almost killed the count, so the duo moves to New Orleans to recuperate. There, Renfield discovers a 12-step self-help group for persons in co-dependent relationships and plans to hunt out the group’s abusive lovers so he can kill and give them to Dracula to feast on without feeling remorse. On following one to a warehouse with stolen drugs, Renfield is confronted by several criminals before they are all attacked by an assassin hired by the rival Lobo crime family.

After killing the assassin, Renfield unsuccessfully attempts to hunt down the man who hired him, Teddy Lobo, who drives off in a hurry, and a weakened Renfield drags the corpses back to Dracula’s lair in the basement of the dilapidated Charity Hospital. Teddy runs into a sobriety checkpoint that is run by Rebecca Quincy, a second-generation police officer, who arrests Teddy after he hurls bricks of cocaine at her. At the police station, Teddy is released from custody by corrupt police officers, while Rebecca has a confrontation with her sister Kate, an FBI agent.

Dracula tells Renfield that the criminals he has brought as food are insufficient, and that the vampire desires the blood of someone pure and innocent instead. Renfield goes to a restaurant to abduct commoners while Rebecca is also led there by clues from the crime scene. The two are caught in an attack on Rebecca’s life that Teddy has been pressured into making so that the fierce reputation of the Lobos will be reestablished. Instead, Renfield and Rebecca defend themselves, killing several gang members and leading Teddy to escape.

Teddy’s mother, Bellafrancesca, orders him to hunt down the man who killed her footsoldiers, and he ends up encountering Dracula when Renfield is away. The two agree to form an alliance while Renfield has taken to heart the teachings of his self-help group and decides to make a life for himself apart from his master. Setting up an apartment and changing his attitude to one of helpfulness, Renfield gives a statement to the police to help them try to finally stop the Lobos. However, Dracula learns of Renfield’s betrayal and slaughters the support group members in front of his former minion.

Rebecca appears and finds Renfield surrounded by dead bodies, causing her to arrest him until she is swarmed by corrupt police officers and the Lobos, who also want revenge on Renfield. Rebecca refuses to hand Renfield over, and she barely escapes with him, getting shot in the process. The next morning, Rebecca finds that Renfield has saved her life, and he explains his true origin while confirming that he wants to reform himself. The two fight through a group of corrupt police officers and Lobo henchmen that come to the apartment to kill them and escape, but after attempting to call Kate, Rebecca discovers that she’s been taken hostage by Dracula and Bellafrancesca. She and Renfield stockpile weapons and bugs to storm the Lobos’ headquarters, only to find that Dracula has empowered over a half-dozen gang members, including Teddy, to have all of Renfield’s supernatural abilities.

After a fight, Renfield kills Teddy. Rebecca heads to stop Dracula, only to find that Kate is beaten to near-death and only the healing properties of Dracula’s blood can save her, which he will offer in exchange for Rebecca’s loyalty. She tricks Dracula by pretending to agree and then injuring him by exposing him to sunlight, leading to him having a final standoff with Renfield and Rebecca that ends with the two collaborating to capture him in a magical circle.

Renfield and Rebecca beat Dracula into pieces, capture his healing blood, and divide up the bits of his corpse into pieces of concrete that they scatter across the water system, either finally destroying the vampire or at least making it very hard for him to reform his body. Renfield then heals Kate and later resurrects his self-help group friends, feeling empowered to make a new life for himself.