In the last decades, a tendency towards urban tissue densification has been observed to counteract the urban sprawl. Densification may be achieved through more compact built areas, preferring the vertical to the horizontal development of buildings but avoiding bulky high-rise building blocks. This strategy significantly affects several aspects of the microclimate and produces direct and indirect effects on human health and well-being. In this regard, air pollution and heat stress constitute two increasing threats to human health and well-being that need to be faced immediately. The involved phenomena are various, intertwined, and may lead to conflicting results. Hence, regenerating existing, well-structured, and stratified urban areas by densification is not an easy challenge. Urban ventilation may favor the mitigation of detrimental effects of air pollution and heat stress on human life. Therefore, a multidisciplinary methodology is presented for embedding urban ventilation performance evaluation into urban management and planning processes. The scope is to propose a framework for urban renewal plans that is citizens-centered and aims at improving their health and well-being in existing urban areas. The methodology builds upon the performance-based approach and is supported by the conceptual framework and the literature reviews provided through the paper.