It's near midnight in downtown San Francisco, and a street musician is getting ready to go home. Unfortunately, it's not the musician's night. As he walks down a dark alley, an attacker emerges and whacks him over the head with a tire iron. But the attacker is not finished. He proceeds to suffocate, poison, stab, shoot, and crush the musician, killing the victim six different ways in all.
Later, across town, Capt. Stottlemeyer and Lt. Disher have called Monk and Natalie to a murder scene at an all-night gas station. Earlier that night, a severely beaten young woman staggered from a nearby park to the gas station, where she collapsed and died. She had been on a date with a doctor she met at a convention. Unfortunately, they don't know the doctor's name, so Monk starts looking for clues. He finds a pair of glasses on the scene that don't belong to the victim, and the search begins for a doctor who's missing his spectacles.
But before the investigation can get going, everyone is called onto a bigger case. The man who killed the street musician left a note identifying himself as the "Six-Way Killer," and the note promises that he will strike again in thirty-six hours. The federal government is taking over the case, and the Deputy Police Commissioner orders Stottlemeyer, Disher, and Monk to assist the man in charge of the federal investigation, Agent Thorpe.
Agent Thorpe arrives in a flashy, high-tech mobile crime vehicle. Thorpe has all sorts of modern gadgets at his disposal, and he immediately clashes with Monk, who is out of touch with modern technology. But Monk stays on the case, and soon he finds himself in the city morgue, where medical examiners are frantically analyzing the body of the Six-Way Killer's victim. Monk, however, is more interested in the untended body of the young woman he was called to investigate earlier, but Agent Thorpe pulls him away. Thorpe wants all the focus to be on the Six-Way Killer.
The next day, with Agent Thorpe continuing to press forward with his intense investigation, Monk, feeling outdated, goes to Julie for help. She teaches him some computer basics, and Monk eagerly shows off his newly acquired skills at the next meeting of the federal task force. Unfortunately, when the task force sets out to raid a suspect's home, a Monk computer error sends everyone to the wrong address, and the feds wind up busting down the door of Julie's friend's sleepover party. A furious Agent Thorpe kicks Monk off the case for his blunder.
With the Six-Way Killer's deadline fast approaching, Agent Thorpe sets a trap for the killer, using Lt. Disher as bait. Monk, meanwhile, is away from all the action with Natalie when he makes a realization that solves the case. Everybody is focusing all their attention on the Six-Way Killer. Who would benefit from this? Answer: the killer of the young woman whose case is being ignored. Monk and Natalie rush to the Medical Examiner's office.
Monk and Natalie arrive at the autopsy room, where they're joined by Agent Thorpe, Capt. Stottlemeyer, and Lt. Disher. Monk explains what's going on. The key to everything is not the street musician who was killed by the Six-Way Killer. Instead, the solution lies with the young woman named Jean Garnett who was found dead earlier that same night. Both victims were killed by the same person, but the street musician and the whole "Six-Way Killer" business was just a diversion. Here's what happened: Jean Garnett met a doctor who took her to a romantic restaurant where they ate an unusual, distinctive desert. Before leaving the restaurant, the doctor paid the bill with a credit card. Later, the date took a violent turn, and the doctor wound up killing Jean Garnett. But once her body was found, the doctor had a problem. During an autopsy, Jean Garnett's stomach contents would be examined, the remnants of the distinctive desert would be found, and the police would be led to the restaurant where the doctor paid by credit card. Those stomach contents could put the murderous doctor away, so he needed a way to delay Jean Garnett's autopsy long enough for her stomach contents to dissolve. The doctor decided to create a diversion - a horrific diversion - the "Six-Way Killer."
Fortunately, Monk has arrived at the Medical Examiner's office in time to spare the incriminating stomach contents. With that key evidence in hand, the killer doctor is easily tracked down and apprehended. Which proves an important point: when it comes to solving crime, the most state-of-the-art, cutting edge technology in the world is... Adrian Monk.