The season follows the story of surgical residents, fellows, and attendings as they experience the difficulties of the competitive careers they have chosen. It is set in the surgical wing of the fictional Grey Sloan Memorial Hospital, located in Seattle, Washington.

The season will take place three months after the events of the last season finale in which Richard and Catherine got married. April and Jackson's relationship has hit the rocks after April has resumed her work overseas in Jordan, leaving Jackson high and dry once again. Callie and Arizona will have new romances.