讲述了阿蒙·蒙克（托尼·夏尔赫布 饰）继续在其特有的精神障碍背景下，帮助警方解决错综复杂的案件。作为前警探，阿蒙在各种看似无法破解的谜团中展现出其非凡的观察力和推理能力，但他极端的洁癖、强迫症和偏执使得他的人际关系复杂多变。在这一季中，阿蒙依然与助手沙宾（比蒂·施拉姆 饰）和好友特纳（贾森·加里-斯坦福德 饰）共同合作，继续侦破各种扑朔迷离的案件。从凶杀案到失踪案，阿蒙每一次都能凭借他的聪明才智和独特视角揭示出隐藏在日常生活中的罪恶。这一季的情节更加紧凑，除了复杂的案件外，还涉及了阿蒙个人生活中的感情波动，深刻刻画了他作为一名侦探与普通人之间的矛盾与挣扎。

Former police detective Adrian Monk (Tony Shalhoub), whose photographic memory and amazing ability to piece together tiny clues made him a local legend, has suffered from intensified obsessive-compulsive disorder and a variety of phobias since the unsolved murder of his wife, Trudy, in 1997. Now on psychiatric leave from the San Francisco Police Department and working as a freelance detective consultant on difficult cases, Monk hopes to convince his former boss, Captain Leland Stottlemeyer (Ted Levine), to allow him to return to the force. Stottlemeyer, who wavered between admiration for Monk and annoyance at his eccentricities during the first season, is becoming more of a friend to Monk as the series develops, frequently calling him in to help, as much for Monk's benefit as for his own. However, he knows Monk's limitations as well as his strengths and may still harbor doubts about the wisdom of allowing Monk to carry a gun or subdue a perpetrator. Stottlemeyer's second-in-command, Lieutenant Randall Disher (Jason Gray-Stanford), also seems to be developing both admiration and compassion for the man he once labeled the defective detective.Despite flaws and inadequacies all around, the three are becoming an increasingly effective team, with additional help from Monk's personal assistant. From the double-episode pilot through the first half of season three, Monk was aided by his nurse, Sharona Fleming (Bitty Schram). But in the tenth episode of the third season, Sharona was replaced by a new assistant, Natalie Teeger (Traylor Howard). Like Sharona, a divorcee with a son named Benjy, Natalie is a single parent, a widow with a daughter named Julie (Emmy Clarke). Unlike Sharona, Natalie is not a nurse but a former bartender with a fresh perspective on Mr. Monk, as she still addresses her new boss.