Mandalay Bay has a tropical South Seas theme. Water features, including numerous fountains, are present throughout the resort. The hotel lobby features a two-story aquarium containing 12,600 gallons of water.

The overarching theme of Mandalay Bay Resort and Casino in Las Vegas is a lush, tropical South Seas paradise. Since its opening in 1999, the resort has utilized a "Mandalay" (Burmese) inspired aesthetic, characterized by gold-leafed windows that glow like a sunset and an 11-acre "Mandalay Beach" water complex featuring real sand, a wave pool, and a lazy river. The interior decor features exotic stone, palm trees, and tropical foliage, aimed at providing a relaxed, upscale "island" vibe that contrasts with the high-energy neon of the Las Vegas Strip. This theme extends to its major attractions, such as the Shark Reef Aquarium, which is themed like an ancient, decaying temple reclaimed by the sea. While the resort has modernized over the years—adding the minimalist Delano tower and the Four Seasons—it maintains its identity as a tropical oasis, focusing on luxury, water-centric relaxation, and a "cool" South Pacific atmosphere that feels more like a resort in Bali than a traditional desert casino.