The call for integrated social-environmental science, complete with outreach to applications and solutions, is escalating worldwide. Drawing on several decades of experience, researchers engaged in such science, completed an assessment of the design and management attributes and impact pathways that lead to successful projects and programs and to understand key impediments to success. These characteristics are delineated and discussed using examples from individual projects and programs. From this, three principal lessons leading to successful efforts emerge that address co-design, adaptive or flexible management, and diversity of knowledge. In addition, five challenges for this science are identified: accounting for change, addressing sponsorship and timelines, appreciating different knowledge systems, adaptively communicating, and improving linkages to policy.