Humans have made profound and irreversible changes to the Earth. The resulting societal challenges of the Anthropocene (e.g., climate change, renewable energy, infrastructure, disasters, pandemics, food insecurity and biodiversity) have causes, interactions and consequences that cascade across a globally-connected, system of systems (SoS). Although we need conceptual strategies and computational tools that enable us to evaluate synergies and trade-offs across multiple systems, current approaches are ineffective and counterproductive. To integratively address these interdependent societal challenges we need an evolutionary SoS approach with a common framework and scientific language, requiring a major transformation in our approach to science and engineering. This workshop will introduce participants to an SoS framework for addressing large-scale challenges of the Anthropocene including research needs, pedagogy, decision-support system, and applications at city and regional scales. Organizers: John Little, Virginia Tech; Amro Farid, Stephens Institute of Technology; Kasey Faust, University of Texas Austin; Megan Harris, Virginia Tech; Lynn Katz, University of Texas Austin; Megan Rippy, Virginia Tech; Lauryn Spearing, University of Illinois Chicago; Peter Vikesland, Virginia Tech; Xiong (Bill) Yu, Case Western