Urban areas are considered net consumers of materials and energy, attracting these from the surrounding hinterland and other parts of the planet. The way these flows are transformed and returned to the environment by the city is important for addressing questions of sustainability and the effect of human behavior on the metabolism of the city. The present work explores these questions with the use of systems analysis, specifically in the form of a Multi-sectoral Systems Analysis (MSA), a tool for research and for supporting decision-making for policy and investment. The application of MSA is illustrated in the context of Greater London, with these three objectives: (a) estimating resource fluxes (nutrients, water and energy) entering, leaving and circulating within the city-watershed system; (b) revealing the synergies and antagonisms resulting from various combinations of water-sector innovations; and (c) estimating the economic benefits associated with implementing these technologies, from the point of view of production of fertilizer and energy, and the reduction of greenhouse gases. Results show that the selection of the best technological innovation depends on which resource is the focus for improvement. Urine separation can potentially recover 47% of the nitrogen in the food consumed in London, with revenue of $33 M per annum from fertilizer production. Collecting food waste in sewers together with growing algae in wastewater treatment plants could beneficially increase the amount of carbon release from renewable energy by 66%, with potential annual revenues of $58 M from fuel production.