The growing scale and complexity of software-intensive systems are introducing fundamental new challenges of uncertainty and scale that are particularly demanding for defense systems. To assist in meeting these challenges, the Department of Defense asked the NRC to assess the nature of U.S. national investment in software research. As part of this study, a workshop was held to examine uncertainty at scale in current and future software-intensive systems. This report presents a summary of the workshop discussions that centered on process, architecture, and the grand scale; DoD software challenges for future systems; agility at scale; quality and assurance with scale and uncertainty; and enterprise scale and beyond. The report also offers a summary of key themes emerging from the workshop: architectural challenges in large-scale systems; the need for software engineering capability; and open questions and research opportunities.