Site-66 Research Institute was a facility conducting groundbreaking research, primarily in biology. However, an unknown incident suddenly occurred, resulting in the deaths of many researchers. The facility's containment systems failed due to a power outage, and all external communications are down. Amidst the unknown and the chaos, the laboratory has ceased to function.

Site-66 is built across multiple underground levels and occupies a vast area including the surface. Some underground sections were still under construction, but all have been abandoned since the incident. As someone connected to the laboratory, Guest must choose whether to get involved or flee.