Rachel van Helsing, descendant of vampire hunter Abraham Van Helsing and Jonathan Harker, operates as a vampire hunter in modern-day Boston alongside Quincy Harker, son of Jonathan and Mina. They recruit Frank Drake, a human descendant of Dracula, to aid their mission to eliminate the vampire lord.

Armed with a crossbow, Rachel relies on her dog Delijah, possessing heightened sensitivity to detect evil, to track Dracula. She participates in extended, largely fruitless searches across the city with Quincy and Frank. Her hunt escalates following Dracula's alliance with a satanic cult and the birth of his son, Janus.

Rachel is present during the confrontation at the cult's church where Dracula's son is accidentally killed. Later, she observes Delores, Dracula's lover, at their son's gravesite and witnesses the supernatural resurrection of Janus as an adult agent of divine retribution.

In the final confrontation, Rachel accompanies Quincy to Dracula's castle in Transylvania. There, Quincy detonates explosives concealed within his wheelchair, sacrificing himself to destroy both Dracula and the castle. Rachel survives this climactic encounter.