Dr. Manning and Dr. Rhodes separately treat complicated cases involving sick babies, only to uncover that the two cases could actually be intertwined. Elsewhere, Dr. Halstead and Dr. Charles treat a homeless man with an upbeat disposition who sheds some valuable insight that prompts one of the doctors to learn a thing or two along the way. Dr. Choi has a Navy corpsman follow him for the day as they deal with the toll of gang violence in the city, while Dr. Reese tries to understand the delicate balance required in her new position.

Dr. Manning and Jeff Clarke are forced to figure out a mystery illness when an Indonesian man who doesn't speak English arrives at the hospital in dire straights. Maggie takes Dr. Halstead to her family reunion. Dr. Rhodes takes on a complicated heart surgery without consulting Dr. Latham. Dr. Reese and Dr. Charles encounter a woman experiencing an unusual pregnancy.

Dr. Manning tends to a young cancer patient and struggles to inform the parents of her dire condition. Elsewhere, Dr. Reese gets contacted by Danny, the troubled young man, and turns to Dr. Charles and Det. Lindsay for help in resolving a difficult situation. Goodwin and Maggie do their best to clear the logjam in the hospital and Dr. Rhodes fine-tunes his instincts after both Dr. Latham and Dr. Halstead pick up on things he doesn't. Meanwhile, a teenage science geek and her friends impress Dr. Choi and Natalie with their bio-engineering lab.

Sharon Goodwin's childhood sweetheart arrives at the hospital, but finds himself in dire straits. To help get his financial footing, Dr. Halstead gets lured into a concierge doctor app idea. Meanwhile, a young woman with a heart infection is treated by Dr. Rhodes against Dr. Charles' advice and Reese's former patient, a sex trafficking victim, reaches out to her for help.

It's a long night on the graveyard shift at Chicago Med, especially for Dr. Reese, who must deal with pronouncing patients dead on more than one occasion. April gets called in to work, much to the dismay of Tate, who pressures her to slow down. Meanwhile, Dr. Charles passes along some vital news to Dr. Latham, and Goodwin asks Dr. Rhodes to work on a most unusual patient.

Dr. Manning and Dr. Charles treat a teenage girl with a rapidly changing set of symptoms that has everyone perplexed. Dr. Choi and medical student Jeff Clark encounter a 19 year-old tough guy who is brought into the hospital in severe distress. Once they establish the cause of the pain, the situation quickly turns dangerous and a resolved Dr. Reese does her best to help. Dr. Halstead must deal with a difficult case that is further complicated by Dr. Stohl, who has a camera crew following him around to shoot a promotional video spotlighting the hospital.

Chicago Med braces for an influx of trauma patients when a pre-dawn pileup finds the hospital in full scramble mode. As a result of the storm and emergencies, supplies become limited and Goodwin, Dr. Manning and Dr. Halstead must deal with making an impossible decision. Meanwhile, Dr. Choi handles a severely burned patient who has one final request and Dr. Charles deals with an agitated patient.

It's a miracle when a trauma patient survives the trip to the hospital, putting the pressure on Dr. Rhodes to keep the man alive. Dr. Choi and Dr. Manning have difficulty diagnosing the location of infection in a paralyzed patient. Dr. Reese must find purpose for a grieving widower who relies on a superhero costume. Meanwhile, April pushes Dr. Halstead to use unproved medications to help a patient with no other options.