Chris (Jesse McCartney), his girlfriend Natalie (Olivia Taylor Dudley), and their mutual friend Amanda (Devin Kelley), are traveling across Europe. They stop in Kiev, Ukraine, to visit Chris's brother, Paul (Jonathan Sadowski), before heading on to Moscow, where Chris intends to propose to Natalie.
Paul suggests they go for an "extreme tour" of Pripyat, the abandoned company town which sits in the shadow of the Chernobyl Nuclear Power Plant. Chris is against going on the extreme tour to explore Pripyat as it's dangerous and would rather stay on the original path in going to Moscow. They meet tour guide Uri (Dimitri Diatchenko), and are joined by a backpacking couple, Norwegian Zoe (Ingrid Bolsø Berdal) and Australian Michael (Nathan Phillips). Uri drives them through the wilds of Ukraine, before they arrive at a Chernobyl Exclusion Zone checkpoint, where they are refused entry by the Ukrainian military. Uri takes them to an abandoned checkpoint he discovered years ago.
The group stops at a river where Uri points out a large, mutated fish apparently able to live on land. As soon as the group distances itself from the river, a school of fish can be seen swimming in the river, meaning that there is still life. The friends are worried about radiation poisoning, but Uri assures their safety with a Geiger counter. After spending a few hours exploring the abandoned city, Uri takes them to the upper floor of an apartment building and shows them the Chernobyl nuclear plant on the near horizon. After hearing noises at the other end of the apartment, it is found to be a bear which runs through the hallway past them, but not harming them.
The group prepares to leave Pripyat and Uri finds the wires in his van have been chewed through. He tries to radio the military for help, to no avail. As night falls, Uri and Chris go out to investigate some noises. Shots are heard and Paul runs out, only to return with Chris whose leg has been severely mauled.
The next day, Paul, Michael, and Amanda go looking for Uri. They follow a trail of blood to find Uri's mutilated body. They take his gun and return to the van. Amanda checks her camera and one of the pictures shows a humanoid creature inside one of the apartment buildings. Natalie stays with the wounded Chris while the others start the 20 kilometer (12 mile) hike to a checkpoint.
Paul, Amanda, Michael and Zoe find a parking lot, where they find parts for the van. On the way back they are chased by dogs and also attacked by mutant fish in a stream. Night falls as the group returns to the van, only to find it ripped to shreds. They find Natalie's video camera, showing that she and Chris were taken by humanoid mutants. While searching for the two inside an old building, the group is chased by more mutants.
During their escape, a traumatized Natalie is found and rescued, but when the group gets distracted by a mysterious young girl, Natalie is captured again. The rest of the group is swarmed by a horde of mutants. While retreating through an underground passage, Michael is captured. As they continue, they find Chris' engagement ring for Natalie, with no sign of Chris. While climbing a ladder, a gang of mutants pull Zoe back down, forcing Amanda and Paul to leave her behind, emerging from the passage right beside the exposed reactor core. Paul recognizes that extremely high radiation levels are causing their skin to blister. They come upon Natalie's body before emerging outside, where they are confronted by Ukrainian military personnel. Blinded by radiation damage, Paul stumbles toward the soldiers, who fatally shoot him.
Amanda passes out and later awaken on a gurney. Several doctors, in protective hazmat suits, inform her that she is in a hospital and they will help her. The doctors reveal that the "creatures" were escaped patients who have been recaptured, Amanda is the only one alive, and cannot be released because she has seen the patients. Amanda is then forced into a dark cell and is swarmed by the escaped patients, as the doctor closes the door's viewing shutter.