The plot of the film follows Ben (Duane Jones), Barbra Cole (Judith O'Dea), and five others, who are trapped in a rural farmhouse in Pennsylvania and attempt to survive the night while the house is being attacked by mysteriously reanimated corpses, known as ghouls or zombies.
Following the scenario set up in Night of the Living Dead, the United States (and possibly the entire world) has been devastated by a phenomenon which reanimates recently deceased human beings as flesh-eating zombies.
Protagonists Roger (Scott Reiniger) and Peter (Ken Foree), two former SWAT members, join with Stephen (David Emge) and Francine (Gaylen Ross), a helicopter pilot and his girlfriend planning on leaving the city, and take refuge in an enclosed shopping-mall.
Dr. Logan (Richard Liberty), the lead scientist on the project, has been secretly using the recently deceased soldiers in his experiments, trying to prove his theory that the zombies can eventually be domesticated.
Taking place shortly after the events of Diary of the Dead, the film follows the actions of former Colonel and current Sergeant "Nicotine" Crockett (Alan van Sprang).
He penned a film treatment with co-writer Paolo Zelati depicting a conclusion to the series that explains the fate of the zombie protagonists from Land of the Dead and an ending where humanity has become virtually extinct.
It was announced in April 2021 that the film had been put back into development under the supervision of Suzanne Romero, with Zelati finishing the script with screenwriters Joe Knetter and Robert L. Lucas.