In The Fourth Deadly Sin, Sanders develops three principal themes: psychology, self-image, and police politics. It is the last one that gets the plot moving. Deputy Commissioner Ivar Thorsen is, as always, embroiled in political intrigues in the New York police department. He has been shepherding his proteges up the departmental ladder to positions of authority, and one of his favorites, Acting Chief of Detectives Michael Ramon Suarez, who is a good administrator but a poor detective, is in trouble because he is having difficulty solving a high-profile murder case; if he fails to solve it by the end of the year, he will not become the permanent Chief of Detectives. To help Suarez, Thorsen turns to former Chief of Detectives Edward X. Delaney, the master of detection, and asks Delaney to run an independent investigation of the murder in order to solve it before year's end, and Delaney, to help an old friend and because he likes to solve mysteries, takes on the task of organizing a small group of police officers into an investigation team.
Psychology as a profession is an important aspect of the mystery. Throughout the novel, psychology is presented as a valuable aid to people who have been marred in some way by their experiences. The murder victim, Simon Ellerbee, is portrayed as a wonderful man who helped his patients cope with their lives and to heal some of their deep psychological wounds. These wounds are primarily important to the plot in terms of self-image. Each of the prime suspects suffers from a poor, even hateful self-image that could have motivated them to kill Dr. Ellerbee — when he revealed too much of his inner self to one of his patients, that patient murdered him in outrage. The blows to Ellerbee's eyes could thus be accounted for — he had seen more of the murderer's self than the murderer could tolerate.
As part of their investigation, the detectives pry into the self-images of the suspects. A few of the officers are bad at this because they cannot see past their own preconceptions of their suspects. One officer suffers a beating in part because he just could not see into the personality of the man he was tailing. Another manages to get over his distaste for homosexuals to understand that the man he was investigating could not commit a violent act. In general, the investigators carefully match alibis against evidence, but they work hard to understand their suspects, in order to develop the motivations of each. This latter effort proves important in eliminating the false confession of a man filled with self-loathing. Their failure to penetrate one person's self-image results in their overlooking the murderer.