The objectives of this study are to diagnose and prevent environmental problems that threaten urban sustainability, the impact of changes in lifestyle (diet, domestic sanitation, and motorization), and production style (agriculture, industry, and services) with the rapid urbanization on regional nitrogen (N) flows, and the water environment was quantitatively evaluated. The megacity Shanghai was chosen as a case study to investigate the temporal changes in nitrogen flow during 1980-2008 by a multidisciplinary approach (a field survey, a regional nitrogen mass balance model, input-output analysis, etc.). Although the total potential nitrogen load in Shanghai has decreased in the 2000s and water pollution problems seem to have improved, the problem has shifted and expanded to affect a wider area through the food/product chain and water/air movement. Further effective solutions that aim at material cycles are necessary and have to be implemented on a large scale.