Metropolitan areas constitute a critical arena in which to protect the environment and handle climate change efforts, both because they are at the root of the problem and they form a suitable working ground to deal with their systemic nature. Using a multi-regional input-output modelling framework, with energy-environmental extensions, this paper proposes a comparative analysis of the Sao Paulo and Lisbon metropolitan areas, distinguishing territorial, production-based and consumption-based responsibilities. This research reveals that the consideration of interregional interactions and leakages to other regions/countries, as well as the appraisal of trade-offs between socio-economic and environmental targets, are critical for climate change policy’s definition and monitoring. The results also stress the importance of tailoring policy measures to the territories and, concurrently, the need for significant changes regarding the discussion of climate change policies on a subnational scale, namely concerning policy concertation and coordination at the global, national and subnational levels.