Seen from Tom's point of view, Tom is put in a truck where Diana, Meghan, Marco and Shawn are. Marco injects Tom with Polonium, thus burning the nano-machines inside him and getting rid of the body snatcher, although it ultimately kills him. Shawn saves Tom by healing him. Tom still has all his memories from being marked and is upset after realizing he has killed people and done bad things. He tells Diana and Meghan that he has to go back to free Collier and that he is the only one who can do it because they don't know he is no longer marked.
Danny goes with his mom to the hospital and notices that people there begin to show the same symptoms and start dying, as if they had taken a promicin shot. Danny realizes that he has developed an ability to spread promicin like a virus, released in the air. Anyone who is around him is exposed to promicin even if they didn't take the shot. He ends up causing hundreds to die but also allows those who survive to develop abilities. He goes to the 4400 center to ask for Shawn's help and to tell him that he is the one killing people and that their mom has also died. Kevin gives Danny an inhibitor so that he is no longer contagious, however this has dire consequences.
Meanwhile people in Seattle are being infected, the outbreak wasn't contained at the hospital and it has spread through the police force as well as NTAC. People start dying and those that don't will soon develop an ability. NTAC is forced to work with Promise City residents to control the violence and chaos that is taking place throughout the city. Those with abilities try to keep order since the federal government has more-or-less written off Seattle, and placed it under heavy quarantine/siege in an attempt to contain the virus.
However, Diana is the only one at NTAC (who has survived) to not test positive for promicin. Marco attributes this to the fact that she was forced to take an early batch of promicin which has somehow made her immune to it; neither dying nor developing an ability. She decides to go to the 4400 center to have Kevin develop some kind of cure to keep others from dying and from coming into contact with promicin. Kevin determines that an enzyme called ubiquinone is what is allowing her to resist promicin exposure. Fortunately, the enzyme is contained in a common over-the-counter drug and Diana sends an order to have supplies of the drug made available to those in Seattle who have not yet been exposed to the virus.
Isabelle is forced to track down Kyle as he has become the new leader of those at Promise City and the marked are not happy. The effects of Danny's ability are ruining their plans to terminate 4400s and prevent people from gaining abilities. Tom returns to try and free Collier. However, he is unsuccessful because upon hearing that Isabelle was sent to kill Kyle he flinched, revealing he was no longer marked. Isabelle was not able to kill Kyle and instead returns to free Tom and Collier and ends up killing the marked there and in return is killed herself. Tom and Collier are able to escape and see how the city has changed. Back at the 4400 center, Danny is feeling the effects of the inhibitor. The promicin is building up in his body since it is no longer being released via his ability. As a result, it is slowly killing him. He tells Shawn that he does not want to stop taking the inhibitor because others will die and he wants to be the last. He begs Shawn to kill him. Shawn, heartbroken, complies.
Seattle has changed with the many deaths as well as giving birth to many who will now develop abilities of their own. The episode ends with Meghan turning a pen into a flower, Garrity creating a perfect duplicate of himself and Marco unintentionally teleporting himself from NTAC to Promise City. It is also revealed that Seattle is now under control of Collier and his followers and is renamed Promise City. Maia remarks to Diana that it is better this way. Kyle visits his father and tells him that even though he has killed people he must move on and leaves him a shot of promicin. The series ends with a finale scene of a welcome to Seattle sign with the word Seattle replaced with "Promise City".