Abstract The microbiome of the built environment comprises bacterial, archaeal, fungal, and viral communities associated with human-made structures. Even though most of these microbes are benign, antibiotic-resistant pathogens can colonize and emerge indoors, creating infection risk through surface transmission or inhalation. Several studies have catalogued the microbial composition and ecology in different built environment types. These have informed in vitro studies that seek to replicate the physicochemical features that promote pathogenic survival and transmission, ultimately facilitating the development and validation of intervention techniques used to reduce pathogen accumulation. Such interventions include using Bacillus-based cleaning products on surfaces or integrating bacilli into printable materials. Though this work is in its infancy, early research suggests the potential to use microbial biocontrol to reduce hospital- and home-acquired multidrug-resistant infections. Although these techniques hold promise, there is an urgent need to better understand the microbial ecology of built environments and to determine how these biocontrol solutions alter species interactions. This review covers our current understanding of microbial ecology of the built environment and proposes strategies to translate that knowledge into effective biocontrol of antibiotic-resistant pathogens.