Patrick and Danelle from Yonkers, New York, go above and beyond to help a schizophrenic patient who's had a hard time being taken seriously in the past. Far away in Austin, Texas, Holly and Chris have a scary run-in with poison control involving a nervous mother. Meanwhile, Baton Rouge, Louisiana, has a busier than usual night with erratic patients, culminating with one of the medics saying, "Only on the night shift."

It's a race against the clock in Baton Rouge for Brandon and Coop to save a man's life after he's been struck by a bullet in the chest. In the middle of an empty parking lot, Austin medics Luddy and Finch encounter the drunkest patient they've ever treated. New Nightwatch Nation team Alyssa and Kasie are called to a special needs pediatric patient in Baton Rouge which reminds Alyssa of her own miracle baby at home.

The opioid epidemic grips the nation as Baton Rouge EMS teams scramble to save lives. A heatwave in the south makes bad calls worse when a man passes out from heat exhaustion and needs intervention before his internal organs shut down. Meanwhile, in Yonkers, Patrick prepares to deliver a baby in the back of the ambulance when an expectant mother's contractions are only 3 minutes apart.

Baton Rouge paramedics rush to the aid of a man attacked by his girlfriend with a box-cutter knife. Gunshots fired in Yonkers send Ariel and Cunningham to save a man down. Meanwhile, in Austin, first responders Kim and Audrey plead with a patient to go the hospital before she has another potentially life-threatening seizure.

In Baton Rouge, a brawl erupts in the back of Meghan and Dee's ambulance when an overdose patient wakes up swinging. Meanwhile, Ariel and Cunningham fear the worst as they rush to the scene of a flaming motorcycle wreck in Yonkers. And in Austin, when a truck swerves out of control, Kim and Audrey hope to find its missing driver at the bottom of a ravine.

In Austin, Texas, a man is shot by someone he trusts and Kim and Audrey must wait until the gunman is apprehended before they can begin treatment. Meanwhile in Yonkers, New York, Cunningham and Ariel face an emotional call that hits too close to home. The Baton Rouge, Louisiana, community is hit hardest tonight when Niki and Nicole are faced with the task of trying to save a life of a fellow service member.

In Austin, Luddy and Finch practice parking lot medicine when they respond to a heroin overdose on a 19-year-old patient. Niki and Nicole show their compassionate side to a young woman suffering from an emotional trauma in Baton Rouge. After the final call of the night, Yonkers medic Alex reveals a sobering truth about her past.

Yonkers first responders Alex and Jamal face unexpected challenges when they respond to a call for a man with a broken ankle who fell from a fire escape. The night really starts to heat up for Steven Lopez and Sam Netheron in Tucson when they are called to a structure fire and must search inside for possible victims. Things get personal for Niki Johnson in Baton Rouge when a call for a patient with back pain takes an emotional turn.