São Paulo is becoming a style setter in fashion, design, film—and food. A writer explores the city's mix of flavors.

The first thing you notice when you walk into the lobby of the Hotel Unique in São Paulo is what you might call a huge "throw bed." The size of a New York City living room, the bed is stitched from dozens of velvet pillowlike tubes which, though they look purple from afar, shimmer in greens and blues and burgundies up close, changing colors like a fish's scales. One night, I asked Humberto Campana, the creator of the one-of-a-kind piece, where he'd gotten the idea.

"What I do comes from the chaos of São Paulo," said Humberto—who, with his brother Fernando, is half of Brazil's most famous furniture-design team—as he lounged on the bed with some friends. Everywhere in this city of 18 million people, the old collides with the new, the rich with the poor, the outrageous with the mundane, and it's these juxtapositions that inspire him.

The Campanas are growing in renown, as is their home city: Four hundred and fifty years after its founding by Portuguese Jesuits, São Paulo has become one of the world's leaders in design, fashion, film and art. Rio de Janeiro may have the beaches, but São Paulo has the more cutting-edge pop culture, the hipper nightlife and the more ambitious restaurants. For the past eight years, São Paulo has hosted Brazil's Fashion Week, and this winter's event featured supermodels like Gisele Bündchen and Naomi Campbell modeling the work of star Brazilian designers, such as Rosa Chá. The annual São Paulo International Film Festival is considered South America's leading venue for new talent. And this fall's exhibition at the Museum of Contemporary Art's Biennial Pavilion—designed by São Paulo modernist Oscar Niemeyer—will bring together more than 140 artists from 60 countries. The museum has what many consider Brazil's finest modern art collection, featuring paintings by Picasso, Kandinsky and Matisse, as well as works by Brazilian artists Tarsila do Amaral and Emiliano Di Cavalcanti.

During the week I spent in São Paulo trying to get a feel for the place Latin Americans call "the New York of the Tropics," I found that comparisons to New York City—or anywhere else on the planet—miss the point. As I looked over the city at night from Skye, the Hotel Unique's rooftop restaurant, São Paulo seemed to contain about 100 different cities. The Hotel Unique, which opened a year and a half ago, is typical of the city's many modernist buildings: an enormous, boat-shaped, copper-and-concrete structure covered with rows of portholes. Through Skye's tall windows, you can see one of the city's landmarks, the wave-shaped Copan apartment building, designed by Niemeyer. You can also see straight down Avenida Paulista, one of São Paulo's main arteries, a brightly lit, mesmerizing stretch of skyscrapers and century-old villas with cobblestoned courtyards. The avenue divides the posh residential areas of Jardins and Pinheiros on the west from Centro, the downtown area, where the Mercado Municipal food bazaar is held every day. To the northeast are the city's three most important ethnic neighborhoods: Liberdade, the Japanese quarter; Bela Vista, which is historically Italian; and the streets around Rua 25 de Março, the Arab quarter, where open-air markets sell Middle Eastern specialties.

That night at Skye, I was accompanied by seven people—Humberto and Fernando, who are of Portuguese-Italian descent, a Spanish-Brazilian businessman from Rio, a Palestinian doctor, two Parisians and one Italian—and the mix seemed typically paulistano. Like the city, chef Emmanuel Bassoleil's menu weaves international influences with Brazilian traditions to create eclectic, exciting combinations. We tried a delicious fillet of sole steamed in Champagne and set atop a puree of yam, a lamb carpaccio drizzled with a mustard-grain sauce and Bassoleil's update of the classic Brazilian moqueca de camarão—shrimp stewed in coconut milk with hot chiles—which he serves in a hollowed-out pumpkin. As a sort of dessert, we ordered pieces of a Brazilian fish from Skye's sushi bar: robalo, a white-meat saltwater fish with the taste of red snapper and the moist texture of yellowtail tuna.

Many of the newest restaurants have sushi bars, a testament to the city's huge Japanese population. São Paulo is home to more Japanese than anywhere else outside of Japan; the majority settled in the first half of the 20th century. As a result, its Japanese food tends to be excellent, whether at one of the yakitori stands in Liberdade or in restaurants like Jun Sakamoto in Pinheiros, arguably the city's best Japanese place. In a long, narrow, quiet space with a sushi bar and two dining rooms, chef-owner Leonardo Jun Sakamoto fuses Japanese and French cuisine to make his own hybrids. One is his signature tuna tartare mixed with foie gras, sprinkled with sake-marinated salmon eggs and served on a thin pool of demiglace.

For every experimental, fusiony menu like the ones at Skye and Jun Sakamoto, there's a restaurant that serves resolutely authentic ethnic cuisine. Some of the best classic Portuguese food is at Antiquarius, in the Jardins neighborhood, a rarefied area of streets lined with tropical trees and beautiful colonial homes standing next to futuristic trapezoidal glass houses. Despite the area's glamorous surroundings—the new Emiliano hotel and stores like Armani, Versace, Christian Dior, Louis Vuitton and the deceptively named Hotel Lycra, a combination restaurant and boutique showcasing different Brazilian designers each month—families come to Antiquarius for homestyle cooking in an elegant but laid-back setting. As soon as I sat down at Sunday brunch, the waiter brought a tray of boiled eggs dipped in a salty red-pepper cream. I ordered minced bacalhau (salt cod) mixed with julienne potatoes and fried egg and sprinkled with pressed hot-pepper oil, along with a Portuguese wine from the extensive wine list, a Luis Pato Quinta do Ribeirinho from Bairrada.

The most outstanding Italian cuisine in the city is at Fasano Restaurante, in the sleek nine-month-old Hotel Fasano in Jardins—a place that's become, in its short life, the epicenter of São Paulo's social scene. During Fashion Week this year, Naomi Campbell and Elettra Rossellini, Isabella's daughter, stayed at the hotel and frequented its lounge, the Baretto; world-renowned Brazilian singer Caetano Veloso has just rented out the penthouse for two years. Still, owner Rogério Fasano has made it his mission not just to create another hip hangout, but also to bring perfectly executed versions of his beloved Italian dishes to São Paulo. Ever since Rogério's grandfather came to Brazil from Milan in 1900, the Fasanos have owned a string of landmark restaurants, cafés and nightclubs in the city, all influenced by the family's Milanese background. Chef Salvatore Loi's menu at Fasano Restaurante, in keeping with Rogério's wish, spans several regional cuisines, including Tuscan, Milanese, Venetian and Sardinian. We tried a delicious homemade ravioli stuffed with duck and served in a duck-broth reduction, as well as hand-rolled spaghetti topped with a delicate ragù of lamb and fresh tomato.

I joined Rogério for dinner one night at Fasano Restaurante; Bebel Gilberto, the bossa nova star, was sitting a few tables away. As her new CD began playing on the sound system, she skipped over to our table and planted kisses on everyone. "The Fasano," she proclaimed, "is the best restaurant in the world!"

On my last night in São Paulo, I met Humberto for dinner at Spot, a restaurant in Cerqueira César, near Jardins, with a menu that fuses European and Asian cuisines. This is one of Humberto's favorite places and a regular stop for design and media insiders. Humberto and I sat listening to loud samba music and eating simple but impeccably prepared dishes—grilled salmon fillet with steamed spinach, linguine with Thai-spiced chicken—and thinking about where we'd go for a nightcap.

São Paulo's nightlife easily rivals that of just about any other city on earth. It's not until after dinner, at around midnight, that things start rolling. I'd already gone with Humberto and his friends to a club called Love Story in Centro; by the time we'd left, at 5:45 a.m., the line to get in extended down the block. After our dinner at Spot, we contemplated going to D-Edge, a new disco on the other side of town, but decided on a relatively mellower option: Baretto, the Fasano's lounge. When we got there at 2 a.m., the crowd was listening to a quintet play "Fly Me to the Moon." As we sat on leather couches, our tuxedoed waiter brought us whisky on the rocks, and Humberto told me about one of his newest creations—an enormous chair, made of hand-rolled bits of carpet and rubber, meant to look like maki. New York City may not yet be ready for chairs like this, but next time I'm in São Paulo, I fully expect to be reclining in one at the city's latest hangout.

Nick Reding, a freelance writer based in New York, is the author of The Last Cowboys at the End of the World: The Story of the Gauchos of Patagonia.