Man plans and God laughs, the saying goes. The line could serve as a motto for novelist Jess Walter, who specializes in mining the cruelties of fate for comedy. His previous novel, 2009's "The Financial Lives of the Poets," tracked an unemployed journalist's ill-fated bid at becoming a pot dealer, and every absurd plot turn read like a proof of life's stubborn unpredictability. "Beautiful Ruins," Walter's superb follow-up, gives that theme a steroid shot: It's a broader, more complex, altogether funnier book.

Time and setting shift so much in the book's early chapters that the novel initially feels centerless, almost recklessly jumbled. But Walter's aim is clear: He wants to show how even today, when the idea of "culture" has seemingly degraded to reality TV and e-mail forwards of cute otter videos, great art can still transform us. First, though, a trip to the past: The novel opens in 1962 as a starlet, Dee, arrives in a desolate Italian port town. She's supposed to be in Rome filming the epic "Cleopatra" with Elizabeth Taylor and Richard Burton, but her pregnancy (by Burton) threatens the already-chaotic production, so she's shunted into lodgings at the curiously named Hotel Adequate View.

Many spokes radiate from this hub. There's Pasquale, a hotelier who looks after and falls for Dee; Michael, a studio staffer who hides Dee, later becoming a Hollywood mogul whose love of plastic surgery has turned him into a "lacquered elf"; Alvis, a sour would-be novelist who names the hotel and later marries Dee; Pat, Dee's hard-luck musician son, unaware that his father is the famous Burton; Claire, a present-day assistant to Michael; and Shane, a desperate screenwriter with a hopeless movie to pitch about the Donner Party.

Got all that? No worries: Walter makes each character memorable, in part by accessing their distinct storytelling voices. We read Shane's heartfelt but gloomy film treatment, Michael's straight-talking memoir, and the first chapter of Alvis' autobiographical novel, which he wants to be "the sort of funny that makes you sad, too." Walter wants that, too: As he moves Pasquale, Michael and Dee toward each other again, decades after their first meeting, the plot is littered with his characters' missed opportunities and dashed ambitions.

Yet "Beautiful Ruins" is enlivened by wisecracks, rude jokes and caustic wit, and if Walter has to choose between cynicism and optimism, he'll pick the latter. "Life is a beautiful catastrophe," he writes; later he'll pay tribute to "the sweet lovely mess that is real life." His characters are long-suffering, prone to failure and sometimes at death's door. But the verve and enthusiasm of this novel, from its let's-go-everywhere structure to the comedy in the marrow of its sentences, are wholly life-affirming.

Mark Athitakis is a reviewer in Washington, D.C. He blogs at markathitakis.com.