Nestled in the Simi Hills, the site was home to Native American tribes who left significant cultural resources, including painted caves and other ceremonial evidence. The Burro Flats Painted Cave on federal government property is listed on the National Register of Historic Places (NRHP) and the California Register of Historic Places (CRHP). NASA, on behalf of local tribes, submitted a nomination to the NRHP to list the entire 2,850 acres as a Traditional Cultural Property, which means the site is associated with cultural practices and religious beliefs of a living community.
Santa Susana also shaped the modern world by technological breakthroughs as a rocket engine test and energy research site for federal government programs. The site was used for rocket engine testing for NASA and energy research, including nuclear, solar and sodium reactor technology, for the U.S. Department of Energy.