Drew stressfully adjusts after returning from deployment in Afghanistan. A bride and her wedding party are treated for injuries sustained during the festivities, and Topher's demanding mother pays a visit.

As the city erupts in violence over an impending jury verdict, the night shift becomes ground zero when they have to take in the man suspected of the racially-motivated shooting at the source of the unrest. His presence in the emergency room sparks sharp conversation and disagreements among the staff over the highly-charged topic and even close friends Kenny and Paul find themselves at odds. Topher does his best to control the mounting chaos in the ER while out in the field, TC makes a decision as to which of two patients to bring in, leaving Paul and Scott to question TC's motives.

Shannon and Jordan venture out for some fun at a local wrestling event only to find themselves treating people on site when a fight breaks out amongst the audience. Back at the hospital, Sam attends to a marathon runner who has collapsed from the heat and things start to heat up even more when the air conditioning breaks. Meanwhile, tensions between TC, Jordan, Sam, and Annie start to boil.

A fireworks explosion creates chaos at a concert, sending patients streaming into the hospital as TC and Topher race to the scene. Syd returns from Afghanistan and faces her unique family dynamic. Jordan and Scott address simmering differences.

The doctors race to save Topher's mom when she comes to the ER with life-threatening symptoms. The team discovers a gravely injured foster mom is harboring a secret. Jordan asks T.C.'s girlfriend for help with a patient.

When a bomb explodes outside the hospital, TC, Topher and Drew are forced to make the tough decision to stay and treat the injured or evacuate and begin transfers to nearby hospitals. Everything changes when TC suddenly realizes he may know the person responsible for the explosion. While the team works feverishly to tend to the wounded, the nurses go on strike just when the hospital needs them the most. Meanwhile, throughout the intense night shift, Shannon and Paul attempt to confront each other about something personal.

TC and Paul pull out all the stops when a crane collapses on a worker at a busy construction site. As Paul works tirelessness to save the crush victim, an observer falls into a deadly gravel pit. TC throws himself into the pit and races to save the patient before he's swallowed by the shifting gravel. Back at the ER, Scott is shaken as the teenage boy he paralyzed returns to the hospital with new complications. Jordan lends support as the emotional case exposes complicated feelings from the past. Meanwhile when a life-saving donor matches with cystic fibrosis patient, Brianna, Drew determines the depth of his feelings for her.

TC initiates a bar brawl, landing him and Drew in jail for the night. While behind bars, Drew and TC's relationship reaches a breaking point. Jordan rushes her date to the ER, where she's shocked to learn he's not who she thought he was. Topher fights for a patient who many doctors have dismissed. Scott and Annie struggle to save their relationship while Jessica works to win back TC's trust. Meanwhile, Syd meets Brianna, and Rick visits the hospital.

In part one of this two-part season finale, Scott and Jordan face grave danger during a rescue mission at a rapidly spreading wildfire outside San Antonio. Tensions are high between Syd and TC as they find themselves in the middle of a humanitarian crisis on the Syria-Turkey border. Paul and Shannon argue over treatment for a patient. Meanwhile a major setback threatens Drew's adoption plans for Brianna, Topher struggles to find a buyer for the hospital and medication goes missing.

Scott and Jordan must perform surgery in the field as the burning wildfire gains intensity around them. Syd has caught Typhus along with hundreds of other patients on the Syria-Turkey border, and TC goes to great lengths to get the medication. Meanwhile, Drew and Rick fight to keep Brianna, while San Antonio Memorial finds an unlikely buyer, though saving the hospital comes at a cost.