This FOA is intended to increase the breadth and scope of topics that can be addressed with systems science methodologies. This FOA calls for research projects that are applied and/or basic in nature (including methodological and measurement development), have a human behavioral and/or social science focus, and employ methodologies suited to addressing the complexity inherent in behavioral and social phenomena, referred to as systems science methodologies. Additionally, this FOA seeks to promote interdisciplinary collaboration among health researchers and experts in computational approaches to further the development of modeling- and simulation-based systems science methodologies and their application to important public health challenges.