After three tours of duty in Afghanistan, T.C. Callahan, M.D. (Eoin Macken), is learning that his toughest job might be right here at home. On The Night Shift, at a San Antonio emergency room, by-the-books hospital administrator Michael Ragosa (Freddy Rodriguez) is newly in charge and tasked with the job of cutting costs and bringing the hospital's doctors in line. T.C.'s not so crazy about that idea, even while he supports his ex-girlfriend and professional colleague Jordan Alexander (Jill Flint), who's angling for the job of head night-shift doctor wrangler. While T.C., Jordan, and a cast of irreverent doctors and nurses care for the patients that crowd their workplace daily, they also carry on their own lives. With goofballs around like T.C.'s BFFs Topher Zia (Ken Leung) and Drew Alister (Brendan Fehr), there are times for pranks, but, when lives are at stake, these doctors are ready for serious business.