Developing a more general science of complex systems will allow us to address questions that pervade and transcend multiple systems (including biological systems such as organisms, food webs, and the human brain, human social systems such as financial markets, formal and informal urban settlements, and social networks) in a more integrated and quantitatively rigorous way, greatly enhancing our understanding not only of the world around us but also of the fundamental nature of reality. Activities include: the development of 1) a more general and predictive theory of complex systems based on a synthesis of the structure and dynamics of energy flows and information processing, and 2) a more rigorous, general understanding and specific application of the crosscutting and interrelated concepts of risk, resilience, robustness, emergence and innovation. Outputs will include: 10 peer review papers per year; five working groups and one workshop per year including a final synthetic workshop in year three. Outcomes: This research agenda has the potential to strongly influence the intellectual foundations, development, and integration of the socio-economic, biological, chemical and physical sciences. Enduring Impact: Although we may not be able to answer all our questions in full, the search for answers will lead to the emergence of significant new questions as well as concepts and principles unveiling ever-deeper aspects of reality.