Fitzgerald began working on a new novel almost immediately after the publication of The Great Gatsby in April 1925. His original plan was to tell the story of Francis Melarkey, a young Hollywood technician traveling on the French Riviera with his domineering mother. Francis was to fall in with a group of glittering and charming wealthy American expatriates (based on Gerald and Sara Murphy and some of their friends) and gradually disintegrate, ultimately killing his mother. Fitzgerald originally intended to call the novel "World's Fair", but also considered "Our Type" and "The Boy Who Killed His Mother". The characters based on the Murphys were originally named Seth and Dinah Piper, and Francis was intended to fall in love with Dinah – an event that would help to precipitate his disintegration.
Fitzgerald wrote several chapters for this version of the novel in 1925 and 1926, but was unable to finish it. Nearly all of what he wrote ultimately made it into the finished work in altered form. Francis's arrival on the Riviera with his mother, and his introduction to the world of the Pipers, was eventually transposed into Rosemary Hoyt's arrival with her mother, and her introduction to the world of Dick and Nicole Diver. Characters created in this early version survived into the final novel, particularly Abe and Mary North (originally Grant) and the McKiscos. Several incidents such as Rosemary's arrival and early scenes on the beach, her visit to the Riviera movie studio, and the dinner party at the Divers' villa all appeared in this original version, but with Francis in the role of the wide-eyed outsider that would later be filled by Rosemary. Also, the sequence in which a drunken Dick is beaten by police in Rome was written in this first version as well (with Francis as the beaten victim); this was based on a real incident that happened to Fitzgerald in Rome in 1924.
After a certain point, Fitzgerald became stymied with the novel. He and Zelda (and Scottie) returned to the United States after several years in Europe, and in 1927 Scott went to Hollywood to write for the movies. There he met Lois Moran, a beautiful actress in her late teens, with whom he had an intense relationship. Moran became the inspiration for the character of Rosemary Hoyt. Fitzgerald supported himself and his family in the late 1920s with his highly lucrative short-story output (particularly for the Saturday Evening Post), but was haunted by his inability to progress on the novel. Around 1929 he tried a new angle on the material, starting over with a shipboard story about a Hollywood director and his wife (Lew and Nicole Kelly) and a young actress named Rosemary. But Fitzgerald apparently completed only two chapters of this version.
By 1930 the Fitzgeralds were again living in Europe. Zelda had her first nervous breakdown in early 1930 and was institutionalized in Switzerland. It soon became apparent that she would never fully recover. Fitzgerald's father died in 1931, an event that was written into the final novel as Dick's father's death. Devastated by these blows (and by his own unrelenting alcoholism), Fitzgerald had settled in suburban Baltimore by 1932 and had finally decided what he was going to write his novel about – a man of almost limitless potential who makes the fatal decision to marry a beautiful but mentally ill woman, and who ultimately sinks into despair and alcoholism when their doomed marriage fails.
Fitzgerald wrote the final version of Tender Is the Night in 1932 and 1933, while renting the La Paix estate from Baltimore architect Bayard Turnbull. He salvaged almost everything he had written for the Melarkey draft of the novel in some form or other and also borrowed ideas, images, and phrases from many short stories he had written in the years since completing The Great Gatsby. Ultimately, he poured everything he had into Tender – his feelings about his own wasted talent and (self-perceived) professional failure and stagnation; his feelings about his parents (who on a symbolic level provided much of the inspiration for Dick and Nicole Diver); about his marriage, and Zelda's illness, and psychiatry (about which he had learned a great deal during her treatment); about his affair with Lois Moran, and Zelda's with the French aviator Edouard Jozan (paralleled in the relationship between Nicole Diver and Tommy Barban).
The book was completed in the fall of 1933 and serialized in four installments in Scribner's Magazine before its publication on April 12, 1934.