Biosphere centers on Billy (Mark Duplass) and Ray (Sterling K. Brown), lifelong best friends, brothers from another mother… and the last two men on earth. Their survival is largely due to Ray, a brilliant scientist who designed a domed structure with all the systems necessary to sustain life on a planet that could no longer support it.

Their custom biosphere is outfitted with basic necessities and creature comforts that make it possible to retain a sense of what life used to be like. A hydroponic garden provides fresh vegetables and a carefully managed fishpond supplies essential protein. Recently, however, fish have begun dying at an alarming rate. With a mere three fish remaining, Billy and Ray face an ominous future. But life may yet find a way.