Vanessa Helsing, a distant relative of the famous vampire hunter Abraham Van Helsing is resurrected, but soon realized that the world was conquered by vampires.Tya is humanity's last hope to lead people to regain their lost.
In the days leading up to "The Rising," Vanessa is attacked and left for dead by an intruder. When Doc discovers anomalies in Vanessa's bloodwork, Axel and the marines come to retrieve the body, only to become marooned in the hospital.
When the hospital's power source is damaged, Vanessa and the survivors only have three hours of reserve power for the UV lights - the only thing keeping the vampires at bay. While Vanessa and Axel head into the ruins of Seattle to scavenge parts, the others are left to fight: against both vampires and amongst themselves.
Vanessa and Mohamad head into the vampire-controlled streets in search of Dylan, the daughter that Vanessa orphaned when she 'died'. Back at the hospital, Cynthia is found dead. Doc soon discovers that what looked like a suicide is actually a deliberate murder. Is there a killer amongst the group? On their return to the hospital, Vanessa is captured by vampires while Mohamad leads a new group of refugees to the hospital.
Vanessa, now in the clutches of Julius and his vampire brood, is forced to demonstrate her powers against someone from her past. Afterwards, she escapes, jumping from the frying pan into the fire. Meanwhile, the refugees discover a serial killer among the other residents, and plot to wrestle control from Axel. In the aftermath, Mohamad is banished from the hospital.
Vanessa and Susan are pursued through the sewers by mutated feral vampires and arrive back at the safety of the hospital only to find the aftermath of a hostile takeover. Vanessa hatches a plan to take it back by force.
Vanessa and Axel lead the others in the hospital's last stand against a siege by Julius and his vampire soldiers. Later when Dmitri's vampire 'Death Squad' arrives, it looks like civil war is brewing among the two vampire factions.
Axel leads the surviving members of their group towards his old military base for shelter but finds it abandoned and in disrepair. With vampires closing in all around them, Axel decides they need a safer refuge and decides to go underground. Separated from Vanessa and the group, Mohamad tries to catch up while navigating hostile territory.
The group is trapped inside 'The Farm' - an underground lab for military experiments - and Vanessa discovers that Axel has been hiding a secret from her that concerns her past. Outside, Mohamad befriends a beautiful girl who doesn't fear vampires. Meanwhile, Rebecca makes a calculated play against the Resistance leadership.
Still reeling from the dire events of 'The Farm', Vanessa and the group find refuge among a band of humans who have bargained with vampires for peace. Their leader, however, appears to be hiding a terrible secret. Meanwhile, the true serial killer among Vanessa's group is finally revealed.