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.

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.

T.C. and Topher return to find Jordan in critical condition and San Antonio terrorized by snipers; Drew and Gwen get caught in the crossfire when a SWAT team corners the snipers.

When protestors descend on a funeral for a dear member of the night shift family, multiple veterans are injured and brought to San Antonio Memorial for treatment. A high profile politician from Drew's past triggers flashbacks to his time in Iraq. Jordan, Scott, and TC disagree on how to best provide care for the politician. Paul and Shannon must improvise while tending to Doug, a former POW. Cain and Drew treat a fearless photographer.

Drew and Paul head to the scene of a multi-car collision while the newly-anointed Dr. Ragosa along with Jordan, Scott, Krista and Kenny, manage the deluge of incoming victims. Meanwhile, TC and Topher head into a war zone to treat an old friend.

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.

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.

A horrific crash sends dozens of soldiers, including Drew's boyfriend, to the emergency room, where TC and Scott clash. Meanwhile, Topher tries to diagnose a soldier's illness, and Kenny tries to improve Ragosa's online-dating profile.

TC and Topher treat the lone survivor of a plane crash while fending off an intimidating law-enforcement officer with a secret motive. Meanwhile, Paul is smitten by an injured exotic dancer whose condition takes a turn for the worse; and Krista cares for a teen with an eating disorder.

A shoot-out in the ER leaves Topher seriously wounded. TC tries to control his Afghanistan flashbacks. An explosion at a fertilizer factory sends burn victims to the ER, overwhelming the shorthanded staff. And Jordan discovers a secret about TC.

A boy is suffering with a serious fever and his high-strung mother begins to show signs of distress.

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.

A violent storm pummels San Antonio, sending numerous patients to the emergency room. Elsewhere, TC and Dr. Scott Clemmens rush to a mudslide disaster to treat a mother and her son; and Topher braves the storm to help his stranded wife, who's going into labor with twins.

A serious car crash results in two teens and a young pregnant woman arriving at the hospital, pushing the night shift members to their limit. Meanwhile, Paul tends to a quirky, wealthy hospital benefactor.

Drew takes action when a gunman attacks at a friend's promotion ceremony.

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.

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.

Jordan and Drew perform a daring rescue by jumping from a chopper. Landing at the nearest VA hospital, Jordan sparks a plan to appease Julian and reunite her night shift team. Back at the hospital, Paul deals with the repercussions of standing up to his father while Scott dives headlong into his professional life. Kenny butts heads with Cain, a traveling nurse with a mysterious past. Shannon indoctrinates Cain as they work in San Antonio Memorial's understaffed and overworked ER. Meanwhile, TC is held captive in Syria. In order to find Syd, TC must treat his captor instead of returning to the safety of an air base with a civilian volunteer, Amira.

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.

Kenny joins Drew at his MMA veteran's support group and finds himself in the fight of his life. Jordan and Cain treat casualties from a hotel fire while Shannon follows a hunch to help save a young victim. Paul's superstar sister, Dr. Bella Cummings, pays a visit to San Antonio Memorial. Meanwhile, TC finally returns home, forcing him to deal with Topher's death.

The night shift is tested when a rancher accidentally shoots his wife. TC heads to a teen party to save the life of a young football star. Jordan and Kenny treat a beauty queen in severe distress. Topher makes a decision about his job.

A downtown gas explosion sends dozens of casualties to San Antonio Memorial Hospital.

Jordan and Krista offer roadside assistance to a motorcycle crash victim.

The overnight crew becomes immersed in a bizarre car-accident rescue. Drew serves overseas in Afghanistan and teams with a colleague to treat an Afghani woman, A spunky grad joins the shift.

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.