As Miss Lonelyhearts reads letters from desperate New Yorkers, he feels terribly burdened and falls into a cycle of depression, accompanied by heavy drinking and occasional bar fights.

Miss Lonelyhearts tries several approaches to escape the terribly painful letters he has to read: religion, trips to the countryside with his fiancée Betty, and sexual affairs with Shrike's wife and Mrs. Doyle, a reader of his column.

In the last scene, Mr. Doyle hides a gun inside a rolled newspaper and decides to take revenge on Miss Lonelyhearts.

"[4] Literature professors Diane Hoeveler and Rita Bernard analyzed the novel through a Marxist lens as a condemnation of Marx's theory of alienation and the colonization of social life by commodification, foreshadowing the stance of the Situationists and Guy Debord in particular.

Miss Lonelyhearts is unable to fulfill his role as advice-giver in a world in which both people and advice (in the form of newspaper ads, for example) are mass-produced.

[7] In 1933, the novella was very loosely adapted as a movie, Advice to the Lovelorn, starring Lee Tracy, produced by Twentieth Century Pictures—before its merger with Fox Film Corporation—and released by United Artists.

Greatly changed from the novel, it became a comedy/drama about a hard-boiled reporter who becomes popular when he adopts a female pseudonym and dispenses fatuous advice.

He agrees (for a hefty payment) to use the column to recommend a line of medicines, but finds out they are actually harmful drugs when his mother dies.

It opened on Broadway at the Music Box Theatre on October 3, 1957, in a production directed by Alan Schneider and designed by Jo Mielziner and Patricia Zipprodt.

In 1958 the plot was again filmed as Lonelyhearts, starring Montgomery Clift, Robert Ryan, and Myrna Loy, produced by Dore Schary and released by United Artists.