The articles in this Special Issue on system change within systems of care (SOCs) provide guidance regarding strategies for modifying SOCs to address the needs of different populations, and ways for changing systems to support more positive child and family outcomes. This paper frames central needs, unanswered questions, and issues that remain for those working to implement SOCs. Specific needs and new directions considered include: (1) rigorous implementation-focused research to identify the necessary and sufficient elements of SOCs and the primary practice approach currently used in SOCs, wraparound; (2) applied research to assess SOCs and document their effectiveness in non-standard or non-traditional settings (i.e., non-mental health settings, including child welfare, juvenile justice, local housing authorities); (3) controlled outcome studies for school-based wraparound initiatives; (4) research to document the effectiveness of the family support efforts that are part of most SOCs; and (5) attention to context, for families, service providers, and collaborative implementation efforts, by researchers and providers alike. Progress in these areas can inform well-targeted system change efforts in the context of SOCs, a critical need given changes in federal funding for these initiatives.