Because so many present and future challenges are regional in scope, regional solutions will be needed, and the next 50 years of research at the regional level will only grow in importance. In the future, appropriate regional scales will be supranational, national, and subnational, many global problems will require localized solutions, and there will be an increasing recognition of the importance of integrating multi-scale human and physical systems models, recognizing that economic and environmental sustainability are inseparable. Models of systems of integrated systems will play an increasingly prominent role. Future modeling research will move away from individual efforts and toward projects that leverage new technologies that support group development and intelligence. The cumulative knowledge-building promise of open source and open science dwarfs that of the individual and small team research silos of the past. The collective development of software tools like Linux, Python and R libraries, and PySAL, to name just a few, is well underway, and fledgling models integrating human and environmental systems are clearly on the horizon. This chapter presents our vision of the path forward in integrated systems modeling, founded on the open source, open science, object oriented modeling triumvirate, using a dynamic interindustry space time economic model to focus the discussion.