Oh, boy. You know it's gonna get real when the setting of anything is Wall freakin' Street.
Now, The Big Short is much more concerned with the economic factors underpinning the 2008 financial crisis than painting pictures for the reader, so there's not much to say as far as physical settings go. Most of the action takes place in nondescript offices littered about Manhattan, though we spend a spell in California and enjoy a quick jaunt to jolly old England.
Still, there are a few moments when the book uses setting to great effect. For example, during the subprime mortgage conference in Vegas, we receive a series of scene description that symbolically relate Wall Street to gambling (which we helpfully analyze over in our "Symbolism" section). This helps solidify the foolishness at the heart of the subprime mortgage market.
Similarly, Vinny and Danny take a trip to Florida to take a look at neighborhoods built by subprime loans, and the sight of so many empty houses makes them realize the extent of the crisis. Although we don't spend too much time in either one of these locations, they help paint a picture of how Wall Street's shenanigans are affecting the world at large.