This paper elucidates eight principles for designing a sustainable circular economy at the urban-regional food-energy-water (FEW) nexus, using a supply chain–linked urban metabolism model. Connecting in- and trans-boundary FEW consumers, producers, processes, and interactions in cities, the model enables analysis of sustainability outcomes related to environmental dimensions, climate vulnerability, human health, and social equity. Our design principles are elucidated by an urban metabolism systems framework and a synthesis of recent works.