Driven by considerations of sustainability, it has become increasingly difficult over the past 15–20 years — at least intellectually — to separate out the water infrastructure and water metabolism of cities from their intimately inter-related nutrient and energy metabolisms. Much of the focus of this difficulty settles on the wastewater component of the city’s water infrastructure and its associated fluxes of nutrients (N, P, C, and so on). Indeed, notwithstanding the massive volumes of these materials flowing into and out of the city, the notion of an urban nutrient infrastructure is conspicuous by its absence. Likewise, we do not tend to discuss, or conduct research into, “soilshed” agencies, or soilshed management, or Integrated Nutrient Resources Management (as opposed to its most familiar companion, Integrated Water Resources Management, or IWRM). The paper summarizes some of the benefits (and challenges) deriving from adopting this broader, multi-sectoral “systems” perspective on addressing water-nutrient-energy systems in city-watershed settings. Such a perspective resonates with the growing interest in broader policy circles in what is called the “water-food-energy security nexus”. The benefits and challenges of our Multi-sectoral Systems Analysis (MSA) are illustrated through computational results from two primary case studies: Atlanta, Georgia, USA; and London, UK. Since our work is part of the International Network on Cities as Forces for Good in the Environment (CFG; see www.cfgnet.org), in which other case studies are currently being initiated — for example, on Kathmandu, Nepal — we close by reflecting upon these issues of water-nutrient-energy systems in three urban settings with quite different styles and speeds of development.