This paper presents a new decision-support methodology and software tool for sustainable management of urban pollution. A number of different methods and tools are integrated within the same platform, including GIS, LCA, fate and transport modelling, health impact assessment and multi-criteria decision analysis. The application of the framework is illustrated on a case study which investigates the environmental and health impacts of pollution arising from different industrial, domestic and transport sources in a city. The example city chosen for the study is Sheffield, UK, and the main pollutants considered are NOx, SO2 and PM10. The results suggest that the absence of the current large industrial sources in the city would lead to a 90% reduction of the SO2 and 70% of the NO2 ground concentrations, consequently preventing 27 deaths and 18 respiratory hospital admissions per annum for a population of 500,000. Based on the total annual mortality and hospital admissions in Sheffield for the year of the assessment, this means that 0.53% of premature deaths and 0.49% of respiratory hospital admissions would be prevented by the estimated reduction in air pollution.