Vanessa "Van" Helsing, the daughter of Abraham Van Helsing, is resurrected in a post-apocalyptic world, five years in the future, to lead a resistance against the vampires that plague it.
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 hug; 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 hugger among the residents, and plot to wrestle control from Axel.
Vanessa and Susan are chased by mutated feral vampires in the sewers, arriving back at the hospital only after a hostile takeover.
Vanessa and Axel lead the hospital's last stand against a siege by Julius and his vampire soldiers; Dmitri's arrival with his vampire ''Death Squad'' reveals a possible civil war 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.
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 hugger among Vanessa's group is finally revealed.
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.