After three years in a coma, Vanessa awakens to a world ravaged by vampires. Now, she and a motley band of fellow survivors fight to stay alive.
Vanessa is once again resurrected and must confront her family's legacy; Axel, Scarlett and the others fend off Blak Tek's forces, who hope to add Scarlett to their list of lab rats.
To find its totem, the First Elder brings Vanessa, Scarlett and Axel to an abandoned insane asylum protected by powerful vampires, where they discover the legacy of a long dead Van Helsing relative.
Vanessa relives the memories of her ancestor, Lily Van Helsing, in Colonial Hong Kong. There, she learns to control her dark side and fights the B'ah, the second vampire Elder.
Sam comes to realize his dark destiny and tries to groom Mohamad to be a worthy partner. Scab and Ivory are bestowed Daywalker powers and return home to find the Sisterhood in ruins.
In San Francisco, Vanessa, Scarlett and Axel find and battle against the Second Elder's forces. In Denver, Flesh, Doc, Julius and Jolene rejoin American civilization as best they can.
Vanessa has a final showdown with the Second Elder in San Francisco. In Denver, Flesh, Doc, Julius and Jolene learn that even in a Safe-Zone, life isn't easy.
Sam moves closer to his destiny while Mohamad tries to free himself from imprisonment. Axel escorts San Francisco survivors to Denver. Ivory and Scab take control of the Daywalker horde.
On a distant island, Vanessa and Scarlett battle the Third Elder which leads Vanessa to make a choice about her path forward, one that Scarlett does not agree with.
Doc and Jolene clash with Denver authorities over the repellent. Flesh chooses to face his past. Axel struggles with leaving Scarlett behind. Ivory and the Sisterhood infiltrate Denver.
Vanessa, trapped in an abandoned slaughterhouse, wrestles between the light and dark sides of her own self before she can move forward on her path to find the Final Elder.
In his hometown, Axel fights both his tragic past and a vicious pack of Daywalkers. Sam can't find Mohamad, and takes his anger out on Chad and Mike.
Scarlett is reunited with Axel but he is badly injured before they can find Vanessa. A mysterious man helps them find their way. Flesh and Jolene are fugitives on the run from Blaktek.