While a few decadesBuilt environment agoArchitecture, it was understoodUrban microbiome that home health was related to the absence of pathogens and sterile environmentsEnvironment, we now understand that the diversity of microorganisms plays a fundamental role in establishing healthy spacesSpace. However, confinement within built spacesSpace—with and without a pandemic—has strongly segregated microbial colonization, affecting immune and metabolic systems. Despite this, a direct reading from the built environmentBuilt environment has not been established since research does not answer the relevant questions for architectureArchitecture, as stated by microbiology. In this way, under the concept of “urban microbiomeUrban microbiome”, this study aims to establish a first characterization of the microorganisms present inside homes in Santiago de ChileSantiago de Chile, based on the collection of microbiological samples in common areas of the house, in areas with certain architectural characteristics, to promote healthy built environmentsBuilt environment from the intersection between designDesign and microbiology. For this, 3 sampling campaigns of bacteria and fungi (with 16S rDNA sequencing and metagenomics) were carried out on interior surfaces, plus the continuous recording of environmental variables in a social condominium in the commune of Renca, particularly in placesPlace of the houses associated with constructive pathologies. In addition, interviews were conducted with the heads of households in the houses characterized by energy poverty. About 20 genera/species of bacteria and fungi were identified. The results show a variable microbiome, highly influenced by its exterior environmentEnvironment and with greater diversity in better-ventilated rooms. The presence of the fungi Aureobasidium pullulans and Alternaria betae-kenyensis, which have been associated with asthma and allergies, in critical placesPlace with poor ventilationVentilation and indoor pollutionIndoor pollution. In this sense, it is evident that the houses’ designDesign, construction and expansion decisions generate impacts on the interaction between the different ecosystems and their built environmentBuilt environment.