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.

After performing a daring on-site rescue to save a teenage girl, Drew is forced to re-evaluate his priorities as a new father. Back at the hospital, the ER is flooded with mass casualty victims from an amusement park disaster. Hoping to get Paul back on staff, Jordan facilitates a rapprochement between Paul and his father. Meanwhile, Scott pursues a more active role in the hospital and Kenny tries to put Cain in his place.

Drew, his mom, and Rick's flight home turns into a medical crisis at 35,000 feet when passengers become sickened one by one. Jordan, Paul, Shannon, Kenny, and Cain spend their day off at an obstacle course fundraiser for Cystic Fibrosis, hosted by Akbar Gbajabjamila. Scott finds himself on a Tinder date he won't soon forget. Meanwhile, TC puts his own life in danger to operate on a soldier.