Iris welcomes an enigmatic ally to their community while Hope questions the visitor's motives. A message upends the sisters' worldview, forcing them to decide between the safety of their home and the uncertainty of the world beyond.
An old friend's heart problems reveal a bigger issue than anticipated; Devon treats a suicidal woman who he thinks might be a good candidate for deep brain stimulation; Billie and Trevor have an emotional reunion.
Dr. Connor Rhodes is reunited with his sister as he treats a family friend; Dr. Natalie Manning must persuade a young musician to undergo a life-saving surgery that could destroy her hearing.
A patient refuses medication for her pain; Dr. Halstead treats a former high school classmate; a pregnant woman has a big reason not to deliver her child.
While the group works together to cross the Mississippi River, a plot to steer the teens back home hits a snag. A member of the group must overcome past trauma to save the others from an approaching threat.