Tana grew up in a world with Coldtowns, places where vampires and those infected with the Cold that creates vampires can be quarantined. Her mother died of the Cold, and her father has been distant ever since. Tana awakes after a night-long party to find all her friends dead, slaughtered by vampires, and her ex-boyfriend infected. She takes her ex, and a vampire who is being hunted by the others, to the nearest Coldtown in an act of desperation. Along the way they meet some more companions, siblings who are headed to Coldtown to try to become vampires deliberately.
Once in Coldtown, several of Tana’s companions are either killed or become vampires, while she waits to see if the injury she suffered in their escape will result in her own infection. Her ultimate goal is just to get home again (although she has an intermediate goal of rescuing a family member when her sister decides to follow her to Coldtown). However, a betrayal by some of her companions (after drugging her), and an unexpected entanglement with the hunted (and very complicated) vampire, interfere with her plans.
The adversary could be seen to be the Cold itself, but also comes in the form of an ancient, elegant vampire named Lucien who threatens what Tana has come to love. Tana does face off against Lucien, but her greatest battle will be with the infection.