ER nurse Jackie Peyton finally confronts her addiction. But when an ambitious new hospital administrator (Bobby Cannavale) joins the staff and starts making waves, Jackie's newfound sobriety is tested to the limits.
It's business as usual at All Saints, except for one small detail: the hospital has been purchased by the multinational corporation Quantum Bay, and the new director -- the handsome-but-serious Mike Cruz -- has arrived for his first day of work with a lengthy to-do list.
Jackie is detoxing in rehab. When she finally wakes, she meets her elderly roommate, an unfriendly klepto named Doris. Meanwhile, back at All Saints, Mike Cruz's innovations continue to irritate the whole staff, except for Coop. In rehab, Jackie escapes to a broom closet for some solitude, only to find the 17- year-old Charlie.
Worried about Grace, Jackie leaves rehab early against the medical advice of her counselor and returns to a very different All Saints. On top of the Quantam Bay takeover, this is the first time she's had to work sober. Almost instantly her nerves are rattled, and even Coop hurts her feelings.
When Grace reveals she knows about rehab, Jackie is blindsided, and goes to Kevin's to make sure he's aware of everything before he hears it from someone else. She's shocked to find a scantily clad woman lounging on his couch when she arrives, but continues on with her confession. Thor and Coop give advice to a man who fears he has broken his penis.
Jackie, making pancakes for the girls, realizes too late that the girls aren't even home--they're with Kevin. At O'Hara's apartment, she admits that she's not adjusting well to living alone and, against O'Hara's advice, decides to call Kevin and invite him to lunch.
Jackie wakes from a vivid dream about sex with Cruz and using again. Kevin, suing for full custody, prompts O'Hara to take action on Jackie's behalf. Jackie and Zoey grow accustomed to their new living situation at the Peyton home, and "co- parenting" duties. Jackie, O'Hara and Akalitus work as a team while treating a transgender teen.
Jackie meets her high-powered divorce lawyer, and is told to play hardball with Kevin if she wants to keep her kids. Eddie becomes an unwilling participant in the Peyton divorce battle. Having a hard time breaking off her engagement to Lenny, Zoey surveys her coworkers for the right breakup strategy.
Jackie comes clean to Cruz about rehab while they tend to an intoxicated Charlie. Charlie bargains with Cruz for Jackie's job, then returns to rehab. Faulty air conditioning puts the entire staff on edge. An 80-year-old admitted for a tonsillectomy shares a bay with a 20-year-old candidate for hip replacement. Coop accompanies O'Hara to her OB/GYN appointment, where she finally leans on him for a little support.
Grace argues with Jackie about enrolling in a new public school. Cruz claims Jackie will mess up again. O'Hara's hemorrhage patient needs surgery but she wants to leave to pick up her father, who slipped and fell. Jackie wants to hire temp nurses because All Saints is understaffed, but Cruz doesn't allow it.
In the Season Four finale, Cruz purposely pushes Jackie to the breaking point and uses her reaction as grounds to fire her, despite the staff's protests. Jackie enrolls Grace in public school. O'Hara goes into labor and Jackie joins her but is soon pulled away when Charlie enters the E.R. as a patient.