We introduce a new ‘multi-layered' indicator set for urban metabolism (UM) studies in megacities. The indicator set is designed for gathering information on the definition (spatial boundaries, constituent cities, population, economy), biophysical characteristics (climate, population density, building floor area), and metabolic flows (water, waste, materials, and all types of energy) of megacities. In addition, it addresses the role of utilities in the provision of services and regulatory actions that, along with public governance, may influence (and/or control) the urban metabolism. In the article, we give background context to the growth and development of megacities, their overarching socio-economic issues, and the definition of their boundaries. Two methodologies to define megacity boundaries are compared, showing that the definition of ‘megacity' is not trivial and that further investigation is needed to establish a baseline for comparison of urban metabolism data. Use of the standardized indicator set will ease inter-city comparisons of urban metabolism, whilst enhancing knowledge of megacities and their transformation into sustainable systems.