Guest satisfaction is often linked to cleanliness in the hospitality industry, however, the complexity of microbial communities colonizing built environments is neglected. Recent breakthroughs in biomedical research as well as environmental science have established that the hotel microbiome--the bacteria, fungi, and viruses on hotel surfaces and in air--dramatically influences traveler health, immunity and wellbeing. This opinion contends that incorporating microbial ecology into hospitality and its future as holobiont-informed design will improve guest health outcomes, promote greater environmental sustainability and set the stage for the next generation of innovation within this sphere of business.