A tiered, system-of-systems modeling framework is required to represent and characterize the interconnections among the many components of socio-environmental systems. However, managing uncertainty and dealing with scale are two major interrelated barriers that must be simultaneously surmounted, because scaling affects uncertainty. In a series of workshops we will: (1) assess current modeling practices in three mature case studies; (2) develop a conceptual system-of-systems modeling framework applicable to all three cases; and (3) quantitatively evaluate implementation of the framework for a selected case study and synthesize conclusions. The workshops will explore promising methods for the treatment of uncertainty and scale within the modeling workflow and framework through tighter integration of model assumptions, analysis, testing, and information propagation among model components. Outputs of the workshops will include high-impact publications in peer-reviewed journals which will stimulate research on design principles enabling new methods to deal with scaling and uncertainty via innovative software and workflow practices, webinars which will communicate workshop outputs to broader scientific and policy audiences, and distribution of workshop findings via organizations such as The Integrated Assessment Society and the Open Modeling Foundation. In addition, two PhD students aligned with the project will contribute to, and be influenced by, the workshops and one will convert the conceptual framework into a working framework as part of his PhD following the workshops. The improvements identified should accelerate progress in understanding and modeling practice of entire families of socio-environmental problems including climate change, disease outbreaks, food/energy/water, coastal flooding and disaster management.