Built environments are, for most of us, our natural habitat. In the last 50 years, the built-up area has more than doubled, with a massive biodiversity loss. The undeniable benefits of a city providing all the basic needs to a growing population showed longer-term and less obvious costs to human health: autoimmune and non-communicable diseases, as well as antimicrobial resistance, have reached unprecedented and alarming levels. Humans coevolved with microbes, and this long-lasting alliance is affected by the loss of connection with natural environments, misuse of antibiotics, and highly sanitized environments. Our aim is to direct the focus onto the microbial communities harbored by the built environments we live in. They represent the nexus for urban regeneration, which starts from a healthy environment. Planning a city means considering, in a two-fold way, the ecosystem health and the multidimensional aspects of wellbeing, including social, cultural, and aesthetic values. The significance of this perspective is inspiring guidelines and strategies for the urban regeneration of the cities of tomorrow, exploiting the invaluable role of microbial biodiversity and the ecosystem services that it could provide to create the robust scientific knowledge that is necessary for a bioinformed design of buildings and cities for healthy and sustainable living.