What Makes Sammy Run? Is the story of the title character, Sammy Glick, who rises during the Great Depression from the bottom of the news media world to become a powerful media mogul. Sammy is shown as sociopathic, greedy, and extremely disloyal. The story is narrated by his sometimes friend Al Manheim, a critic at Sammy's paper. Near the novel's conclusion Sammy, isolated and frightened by success, is shown to repent somewhat, but he quickly backslides into decadence and sociopathy.
Told in first person narrative by Al Manheim, drama critic of The New York Record , this is the tale of Sammy Glick, a young uneducated boy who rises from copyboy to the top of the screenwriting profession in 1930s Hollywood by backstabbing others.
Manheim recalls how he first met the 16-year-old Sammy Glick when Sammy was working as a copyboy at Manheim's newspaper. Both awed and disturbed by Sammy's aggressive personality, Manheim becomes Sammy's primary observer, mentor and, as Sammy asserts numerous times, best friend.
Tasked with taking Manheim's column down to the printing room, one day Glick rewrites Manheim's column, impressing the managing editor and gaining a column of his own. Later he steals a piece by an aspiring young writer, Julian Blumberg, sending it under his own name to the famous Hollywood talent agent Myron Selznick. Glick sells the piece, "Girl Steals Boy", for $10,000 and leaves the paper to go to work in Hollywood, leaving behind his girlfriend, Rosalie Goldbaum. When the film of Girl Steals Boy opens, Sammy is credited for "original screenplay" and Blumberg is not acknowledged.
Glick rises to the top in Hollywood over the succeeding years, paying Blumberg a small salary under the table to be his ghost writer. He even manages to have "his" stageplay, Live Wire , performed at the Hollywood Playhouse. Although the script is actually a case of plagiarism, The Front Page in flimsy disguise, no one except Manheim seems to notice. Sammy's bluffing also includes talking about books he has never read.
Manheim, whose ambitions are much more modest, is both fascinated and disgusted by the figure of Sammy Glick, and Manheim carefully chronicles his rise. In Hollywood, Manheim is disheartened to learn that Catherine "Kit" Sargent, a novelist and screenwriter he greatly admires, has fallen for Sammy's charms. Although Manheim is quite open about his feelings for Kit, she makes it clear she prefers Sammy, especially in bed. When she met Sammy, she told Manheim, she had "this crazy desire to know what it felt like to have all that driving ambition and frenzy and violence inside me."
Manheim also describes the Hollywood system in detail, as a money machine oppressive to talented writers. The bosses prefer to have carte blanche when dealing with their writers, ranging from having them work on a week-to-week basis to giving them a seven-year contract. In the film industry, Manheim remarks at one point in the novel, it is the rule rather than the exception that "convictions are for sale," with people double-crossing each other whenever the slightest chance presents itself to them. Hollywood, he notices, regularly and efficiently turns out three products: moving pictures, ambition, and fear. Manheim becomes an eyewitness to the birth of what was to become the Writers Guild, an organization created to protect the interests of the screenwriters.
After one of the studio's periodic reshufflings, Manheim finds himself out of work and goes back to New York. There, still preoccupied with Sammy Glick's rise to stardom, he investigates Sammy's past. He comes to understand, at least to some degree, "the machinery that turns out Sammy Glicks" and "the anarchy of the poor". Manheim realizes that Sammy grew up in the "dog-eat-dog world" of New York's Lower East Side (Rivington Street), much like the more sophisticated dog-eat-dog world of Hollywood. The one connection between Sammy's childhood days and his present position seems to be Sheik, someone who went to school with Sammy and regularly beat him up. Now Sheik is working as Glick's personal servant (or quasi-slave)—possibly some kind of belated act of revenge on Sammy's part, or the "victim's triumph".
When Manheim returns to Hollywood he becomes one of Glick's writers. There he realizes that there is also a small minority of honorable men working in pictures, especially producer Sidney Fineman, Glick's boss. Manheim teams up with Kit Sargent to write several films for Glick, who has successfully switched to production and moved into a gigantic manor in Beverly Hills.
Fineman's position becomes compromised by a string of flops, and Manheim attempts to convince Harrington, a Wall Street banker representing the film company's financiers, that Fineman is still the right man for the job. This is the moment when Glick sees his chance to get rid of Fineman altogether and take his place. At a reception, Glick meets Laurette, Harrington's daughter; he immediately and genuinely falls in love with this "golden girl," discarding his girlfriend. He feels that he is about to kill two birds with one stone by uniting his personal ambition and his love life.
Fineman, only 56, dies soon after losing his job to Sammy—of a broken heart, it is rumoured. Sammy's wedding is described by Manheim as "a marriage-to-end-all-marriages" staged in the beautiful setting of Sammy's estate. Manheim and Kit Sargent, who have finally decided to get married, slip away early to be by themselves. Sammy discovers Laurette makinglove in the guest room to Carter Judd, an actor Sammy has just hired. Laurette is not repentant: She coldbloodedly admits that she considers their marriage to be purely a business affair.
Sammy calls Manheim and asks him to come over to his place immediately. Once there, Manheim for the first time witnesses a self-conscious, desperate, and suffering Sammy Glick who cannot stand being alone in his big house. In the end, Sammy orders Sheik to get him a prostitute, while Manheim drives home.