Michael attempts to intercept "The Package," but is a bit surprised to find out that it's not material, but a man whose DNA is encoded with valuable information that not only has people who not only want "The Package" as well, but they also want Michael dead.
In order to successfully track an unknown fellow operative's beacon signal, Michael needs to enlist some help when going undercover and the only one who fits the bill is Zoe, much to Sarah's disdain. The mission, however, leads Michael to a trail of illegal weapons trade and a rogue operative.
Everyone enjoys a good Halloween prank, but it's no laughing matter when a laboratory technician shows up dead in the complex, which goes into lock down and it's only then when it's discovered that K.I.T.T.'s self destruct sequence has been activated while in an airplane over the ocean with Sarah and Michael aboard.
Mike and K.I.T.T.'s botched attempt to stop a truck hijacking results in a hi-tech computer virus turned loose and their mission to stop it must be from a distance where it will not affect K.I.T.T. due to its ability to mutate and take over anything electrical, computer, or even metallic.
K.I.T.T., Sara, Zoe and Billy leap into action in an attempt to assist in ending a stand-off of what appears to be a botched bank robbery without the help of Michael, who's one of the hostages inside the bank.
When Mike and K.I.T.T. try to assist in a downed jet aircraft, they find that it leads to a 10 year old boy genius who was under protective custody in cooperation with the DEA, only to find the crash was faked, the boy was kidnapped by a South American drug smuggler, and it all ends up with Mike on the run as a fugitive, himself.
Looking forward to some much needed down-time, Michael returns to his old neighborhood, only to find that the owner of the local bar has died of mysterious causes and the bar scenery has changed also, including several fires in recent weeks.
Mike and K.I.T.T. are trying to track down a stolen serum that maximizes the recipient's physicality before it gets into the wrong hands. With the help of the lab's research assistant, Billy learns some information about the serum that will help Mike when he takes on the now powerful thief. Meanwhile, Sarah is overwhelmed with her new duties and quickly learns how much work it will take to re-institute the Foundation for Law and Government.