Immortal warrior Blade continues his fight against a shadowy underworld of vampires who are threatening total domination of mankind. Blade's latest pursuits take the half-vampire to his hometown of Detroit where he meets Krista, a recently dispatched U.S. military combat medic who is investigating her brother's suspicious murder.

As Krista is pulled into the underworld, she teams up with Blade and his partner Shen to infiltrate the vampires from the inside and out. However, Blade has to keep strict tabs on Krista, who could easily succumb to the dark forces of the underworld she now inhabits.

When Marcus keeps Krista from leaving the House of Chthon, she is forced to make her way without the help of Blade or Shen. With Krista unavailable to him, Blade seeks proof of Marcus' vaccine through Reverend Carlyle, a link to the "asher" community. Marcus explains the rules of all the Houses to Krista.

Blade pursues a contact in the House of Armaya who has information on Marcus's experiments. Krista accompanies Chase to an AA meeting for an unexpected meal. Krista tells Blade about the vaccine called Aurora and agrees to procure a sample. FBI Agent Ray Collins' investigation of Trooper Hirsch's murder leads him to Boone.

Blade pays a visit to suspicious gynecologist Dr. Vonner. Reverend Carlyle sets Blade up to encounter the Bad Bloods, disenfranchised vampires Blade first turned and who were once his childhood friends. Chase takes Krista to the House of Leichen for a blood ritual that will help them track Boone.

Boone continues his killing rampage and pays a visit to Damek at the House of Armaya. Krista learns Boone's whereabouts as well as his hostage Patricia. Charlotte, the diminutive head of Chthon, confronts Marcus about Aurora. Chase attacks Boone so Marcus sends her to Berlin to track down the pregnant patient, Vanessa, but its a race with other Familiars to get to her first. Blade kidnaps Vanessa. Krista tries to steal the vaccine.