In the Syrian desert, female vampire Danica (Parker Posey) leads a team of similar people to go deep into the ancient desert palace, intending to awaken the sleeping vampire king, Drake (Dominic Purcell). In the night, Blade (Wesley Snipes) is still fighting endless battles with vampires, but he soon falls into Danica's trap and kills a human by mistake, so he is arrested by FBI agent Wilson and others. At the same time, Blade's old partner Whistler's daughter Abigail (Jessica Biel) and young people such as Hannibal King (Ryan Reynolds) hold similar beliefs to Blade and form a team to use themselves as bait to eliminate vampires. They rescue Blade from the FBI and Danica, but the latter sneers at their audacity. However, facing the powerful vampire king Drake, they have to fight side by side...