Megacities consume a large amount of energy and materials, leading to various environmental impacts. In this paper, multi-scale integrated analysis of societal and ecosystem metabolism (MuSIASEM) is applied to compare and analyze the metabolic characteristics of four global megacities. This paper extends the analytical framework of MuSIASEM to the N-3 level (detailed industries) providing a higher level of details than current applications. Based on model results, among the four global megacities, Shanghai's labor productivity and energy efficiency are lowest given its large manufacturing sector and complex industrial structure. Tokyo's labor productivity is the highest with a productive tertiary sector. London has the lowest exosomatic energy metabolic rate and a mature tertiary sector. Paris has the best social welfare system. Such results highlight key factors affecting the metabolic pathways of the respective cities and provide city planners and policy-makers critical information to support green growth and low carbon development.