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The borders of SOMA are Market Street to the north-northwest, the San Francisco Bay to the east, Townsend Street to the south-southeast, and U.S. Route 101 (Central Freeway) to the west-southwest. It is the part of the city in which the street grid runs parallel and perpendicular to Market Street.

During the mid-19th century, SOMA was a residential enclave for the rich that centered around the Rincon Hill area. The neighborhood changed by the turn of the century as a result of heavy industrial development caused by the proximity to the docks. Instead of an area for the rich it was transformed into a slum containing sweatshops, power stations, flophouses, and factories.

Following the 1906 quake, the area was rebuilt with wider than usual streets, as the focus was towards the development of light to heavy industry. The construction of the Bay Bridge and the U.S. Route 101 during the 1930s saw large swaths of the area demolished including most of the original Rincon Hill.

The area was transformed yet again during 1970s and in the early 1980s with the construction of the Moscone Center, which occupies three blocks and hosts many major trade shows.

In addition, the opening of the San Francisco Museum of Modern Art in 1995, the Mission and Howard Street area of the South of Market has become a hub for museums and performances spaces.