U.S. national security depends on defense software that is secure, reliable, and agile. At the request of the Defense Advanced Research Projects Agency (DARPA), the National Academies of Sciences, Engineering, and Medicine conducted a study to explore how to enhance the assurance and agility of large-scale, integrated software-based systems. This report recommends ways the Department of Defense can engineer and manage its software systems to reduce cyber risk and enable more rapid system evolution to meet changing mission needs.