Today's South San Francisco owes its origins as "The Industrial City" to meat packer Gustavus Swift, who established his cattle stockyards in the area in 1890. Others followed and business boomed due to a large ship-building industry during the two World Wars.

Since 1976, South San Francsico has been home to Genentech Inc. one of the world's largest and first biotechnology companies. Its waterfront compound continues to expand.

Several housing units are being built across the city, along with a major ongoing development on the hill west of Highway 101. Oyster Point Marina features a 600-berth pier area for commercial fishing boats and live-aboard vessels. The city is home to many parks and a weekend farmer's market, and the private California Golf Club is located on W. Orange Avenue.