Population urbanization is a global trend, and socioeconomic activities in urban areas cause changes that affect the environment and human well-being beyond the specific territories, thus connecting urban to non-urban areas and creating city-regions. This article's objective, from an ecosystem perspective, is to gather a set of information on municipalities (counties) belonging to the Middle Paraíba River Valley Region in the State of Rio de Janeiro, Brazil, in order to identify conditions and trends in environmental sustainability and well-being. The conceptual framework adopted here was that of the Millennium Ecosystem Assessment, identifying direct and indirect driving forces that affect human well-being, with health as a component of the latter. We used a set of available public-domain data and information sources on the municipalities, grouped by socioeconomic and environmental conditions and the soundness of institutional structural well-being for sustainability. The indicators used here point to a process of degradation in the ecosystem services that has still not been prevented by the prevailing institutional structure, thus increasing constraints on well-being and the spread of socio-environmental impacts in the middle and long terms.