Vanessa Helsing, a distant relative of the famous vampire hunter Abraham Van Helsing is resurrected, but soon realizes 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 all hell breaks loose outside the building.

The hospital's power source is damaged, jeopardizing the protective UV lights. Vanessa and Axel head into Seattle to scavenge parts, leaving the others to fight against the vampires amongst themselves.

Vanessa and Mohamad head into the vampire-controlled streets in search of Vanessa's daughter; Cynthia is found dead at the hospital, and Doc thinks her apparent suicide is actually a deliberate murder; Vanessa is captured by vampires.

Vanessa, now in the clutches of Julius and his vampire brood, is forced to demonstrate her powers; the refugees discover a serial killer among the residents, and plot to wrestle control from Axel.

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 an underground lab for military experiments, and Vanessa discovers that Axel has been hiding a secret about her past; Mohamad befriends a girl who doesn't fear vampires; Rebecca makes a calculated play.

Vanessa and the group take shelter in Susan's family farm, where drastic action is taken against Sam; Rebecca's latest experiment to create Daywalkers fails, and Dmitri's patience grows thin.

While on the road to a vampire-controlled camp, Vanessa and Mohamad find themselves in a dangerous game of cat-and-mouse against Sam. Sheema discovers a secret that can bring down the ghetto-cell of the Resistance, while Julius takes a clandestine meeting with Dmitri. Ultimately, Vanessa and Mohamad walk into a trap that places one of them in great peril.

Now in Dmitri and Rebecca's clutches, Vanessa learns secrets from her past and finds herself at a crossroads; Flesh and the Resistance accelerate their timeline to rescue Vanessa; Mohamad and Sheema finally come to blows over their allegiances.