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There were 20,870 housing units at an average density of 2,283.1 per square mile (881.6/km²).

There were 20,118 households out of which 39.2% had children under the age of 18 living with them, 51.8% were married couples living together, 11.2% had a female householder with no husband present, and 28.5% were non-families.

The micro climate of South San Francisco is dominated by wind from the nearby Pacific Ocean, which typically keeps the daytime temperatures quite cool year round, even during the summer months.

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The major manufacturers closed, and new development was focused on office parks, housing, high-rise hotels, and yacht harbors.

The biotechnology giant Genentech opened in 1976, leading to South San Francisco's new identity as "the birthplace of biotechnology".) of it (69.69%) is water.

South San Francisco lies north of San Bruno and San Francisco International Airport in the Colma Creek valley south of Daly City, Colma, Brisbane, and San Bruno Mountain; east of Pacifica and the hills of the northern Coast Range lying along the San Andreas Fault; west of the waters of San Francisco Bay.

The population grew from 4,411 in 1920 to 67,009 in 2014.

It has tripled since World War II with the opening of such subdivisions as Buri Buri, Winston Manor and Westborough on the slopes west of El Camino; The city is particularly noted for the South San Francisco hillside sign on Sign Hill, which rises to the north of the city, with large white letters that proclaim "South San Francisco, The Industrial City".

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