The early 1930s. Palm Beach, Florida. Addison Mizner is on a bed, surrounded by trunks, packing crates, old furniture and people. He promptly dies. The door to one of the packing crates flies open, revealing Wilson Mizner, Addison's brother. The people begin to berate Addison for making a waste of his life ("Waste"). Addison and Wilson start to squabble like children until they are interrupted by Mama Mizner... and the scene shifts to their father's deathbed in the early 1890s. Papa admonishes the boys that America is now their nation to mold ("It's in Your Hands Now"). Papa then dies and Mama reveals that the family is broke. Addison, Wilson and Mama are considering what to do next when a prospector appears, proclaiming the Gold Rush in the Yukon ("Gold!"). Addison doesn't like the sound of it, but Mama is enthusiastic and Wilson persuades him.

In Alaska, Addison and Wilson are luckless, miserable and freezing. When Wilson's sleeping bag rips, Addison offers to share his. Huddled awkwardly together, the brothers reminisce about their shared childhood ("Brotherly Love"). A frustrated Wilson leaves for town to get supplies, where he is drawn into a poker game by a gang of cardsharps ("The Game"). Wilson is green but picks the game up quickly. He's winning when Addison appears, irate about being abandoned. Addison has, however, finally found gold. Wilson persuades him to bet their claim by explaining his newfound philosophy. They win, but the ghost of Papa appears to chastise Addison for tawdry behavior. Wilson trades the claim for the saloon, which infuriates Addison, who then takes his share of their winnings and storms off.

Seeking to make his own fortune, Addison embarks on a peripatetic adventure, traveling from Hawaii to Bombay to Hong Kong to Guatemala. Each business venture he tries turns into a disaster, and he is left with only a pile of souvenirs. Slowly, he realizes that he has a talent for arranging these disparate knickknacks – an artist's eye for design – and vows to build a house to hold them all ("Addison's Trip"). Wilson and Mama appear. They've been having their own adventures, traveling across the country. The two catch up with Addison in New York City, where he has his first architectural commission: a pool house for wealthy widow, Myra Yerkes. Before Addison can complete the deal, however, Wilson woos Myra and marries her, then proceeds to squander her fortune on a variety of risky ventures, all in a whirl of alcohol, cocaine, women and publicity ("That Was a Year").

In the meantime, Addison has been caring for ailing Mama. Increasingly frustrated that he can't get Wilson to visit her or pay him for his pool house project, Addison listens as Mama explains her adoration for her prodigal son ("Isn't He Something!") Mama dies just as Wilson finally arrives, high on drugs. He reveals cheerfully that Myra has tossed him out, which coincidentally means the end of Addison's commission. In revenge, Addison cruelly allows Wilson to discover Mama's body. Wilson is horrified, the brothers fight and Addison throws Wilson out.

A real estate agent appears – the spiritual twin of a Yukon prospector – announcing a real estate boom in Florida ("Land Boom!") Addison heads south on a train, where he meets handsome young Hollis Bessemer, who has just been disowned by his industrialist father. He's headed to Palm Beach, where his aunt and uncle are looking for a place to build a house. Hollis hopes to build an artists' colony and needs their support ("Talent"). Addison tags along with Hollis and charms his aunt, Eva Stotesbury, into hiring him as her architect. The extraordinary house that he builds touches off a mansion-building competition among rivalrous rich families ("You"). Hollis and Addison make a good team, both in business and in love ("The Best Thing That Ever Has Happened").

Addison becomes addicted to success and cocaine. When a down-and-out Wilson appears, begging for favors and forgiveness, Addison rubs his face in it. Wilson collapses ("The Game – Reprise"). During his recovery, Wilson persuades Hollis to embrace his original impulse to be a patron of the arts. They then go to work on Addison, who is won over and begins designing a utopian metropolis ("Addison's City"). Hollis provides funding, and Wilson becomes a consummate pitchman for the soon-to-be built dream city of Boca Raton. Everything spins out of control, with Wilson making increasingly gaudy and fraudulent promises, and Addison supporting him ("Boca Raton"). Finally, when Hollis challenges Wilson, and Addison sides with his brother, Hollis withdraws his money and support, walks out on Addison and the project collapses. Addison, realizing that he has once again been a willing patsy in one of Wilson's schemes, screams at him to leave ("Get Out"). Wilson counters with his own emotional pragmatism ("Go").

We transition back to a bed, where Addison is dying... just as he did at the beginning. A packing crate flies open, and Wilson emerges. This time, however, he's as dead as his brother. He joins Addison in bed and, as best as they can, the brothers finally reconcile ("Finale").