At the heart of Once in a Lifetime lies the steadfast friendship between May, George, and Jerry. From the outset, they remain united—even sharing a single bank account. The trio previously had a vaudeville act, which Jerry decided to sell, believing they had better prospects in Los Angeles. Although May, and to some extent George, were unhappy that Jerry made such a significant decision without consulting them, they ultimately chose to support it. May devised the plan for their elocution school, used her contract to launch it, and handled most of the operations once it opened.

Despite the challenges their friendship faces in Hollywood, it endures. May grows somewhat resentful of having to shoulder most of the work and feels that Jerry, whom she loves, has become absorbed in the fast-paced lifestyle. George feels frustrated, sensing that the other two don't fully appreciate his intelligence or abilities. Jerry becomes temporarily unaware of his duties toward May and George. However, when adversity strikes, they come together to support one another. After George is named head of the studio and insists on hiring May and Jerry as well, the pair stands by George when he truly needs their help. By the play's conclusion, their bond is as strong as ever. Once in a Lifetime underscores the value of these relationships in an unpredictable world.

In Once in a Lifetime, a theme of hope and optimism runs throughout the story. Regardless of the challenges faced by May, Jerry, George, and most of the other characters, they consistently maintain a positive outlook for the future. Jerry is confident that he, May, and George will find success in Los Angeles. George believes that Susan will become a successful actress. Their optimism is rewarded as both of their dreams are realized. Even the aspiring film industry hopefuls—actors, actresses, and scriptwriters working in the hotel—are confident about their futures in the movie business.

The sole character seemingly devoid of hope is Lawrence Vail, an underutilized playwright and screenplay writer, who is passed around in an attempt to discuss his work with someone at the studio. Vail is frustrated because, despite receiving a paycheck, he hasn't been given any writing assignments. Although he is exasperated by the endless runaround, Vail still believes that a better life awaits him. He was content as a playwright in New York City, and in Act III, he returns home after a brief stay at a sanitarium designed for playwrights like him. Once in a Lifetime presents a boundless optimism that starkly contrasts with the economic conditions in the United States at the time, reflecting the upbeat spirit of the Jazz Age of the 1920s, prior to the onset of the Great Depression.

Aligned with the concept of optimism, the theme of success and failure plays a crucial role in Once in a Lifetime. Almost every character experiences some form of success in the play. True failures are rare, with Lawrence Vail being a possible exception, yet his failure is merely not securing a meeting. Nonetheless, he still receives payment without performing any work. May, Jerry, and George’s elocution school at the studio does not succeed, leading to their dismissal; however, this setback is only temporary. By confronting the studio owner, Herman Glogauer, George secures a position as studio supervisor and ensures his two friends are rehired as well.

Although George lands himself in tricky situations as studio head—such as being fired when Glogauer discovers he ordered the wrong script to be filmed and when he purchases 2,000 airplanes for the studio—he manages to keep his role and cements...