In a post-apocalyptic world overrun by zombies, a geeky and anxious college student known as Columbus has survived by adhering strictly to a set of personal survival rules. While trying to make his way to his hometown in Ohio to see if his parents are still alive, he encounters Tallahassee, a rough and tough zombie-slayer with a fondness for Twinkies and a personal vendetta against the undead. The unlikely pair decide to travel together, benefiting from each other's company and survival skills as they make their way through the desolate landscape littered with the carnivorous creatures.

During their journey, they meet Wichita and Little Rock, two sisters who are also adept at navigating this dangerous new world. The sisters initially con the men, but circumstances eventually force the group to team up. As they continue to head east, their makeshift family must confront their personal quirks and the various threats that emerge, both living and undead. The importance of trust and friendship is tested as they rely on each other to survive the zombie-infested America, all while searching for a sanctuary free from the chaos.