People typically spend approximately 90% of their time indoors, making indoor spaces a vital habitat. Coexisting with the occupants in indoor spaces are communities of bacteria and fungi, collectively termed the built environment (BE) microbiome. This classification can also be extended to include the virome, encompassing all viruses. Indoor environments thus hold significant health implications for their occupants, including the potential spread of pathogens, asthma, and allergies. Advances in nucleic acid sequencing technologies have improved our understanding of the diversity of bacteria and fungi in BEs and the factors influencing their composition. However, the diversity and metabolic functions of viruses and their interactions with microbial hosts in BEs over time and under different environmental conditions remain poorly understood. A comprehensive understanding of the characteristics of all microbial life in BEs is of particular relevance to the health of indoor occupants, especially in densely populated regions such as Hong Kong, which has one of the world’s highest population densities. Such knowledge is crucial to facilitate the creation of a safer and healthier indoor BE microbiome and virome for the occupants. Through the proposed project, we will aim to enhance our understanding of viruses and virus–host interactions in BEs. We will use occupied residences in both urban and rural neighborhoods of Hong Kong as model systems and will apply state-of-the-art metagenomic and metatranscriptomic sequencing methodologies to characterize the diurnal variations in microbiome and virome compositions on frequently and infrequently touched surfaces, both in the summer season with mechanical ventilation and the winter season with natural ventilation. We will assess the environmental conditions of indoor air and surfaces and correlate them with microbiological data. The taxonomy and metabolic functions of bacteria, fungi, and DNA viruses will be determined using DNA sequencing, whereas metabolically active bacteria and fungi and their transcribed metabolic functions, as well as RNA viruses, will be identified using RNA sequencing. We will elucidate the mechanisms and extent of the virus–host interactions and how these interactions vary over time and under different environmental conditions. Preliminary field results support our hypothesis that the taxonomic compositions and metabolic functions of the microbiomes and viromes, as well as their interactions on surfaces strongly, correspond with indoor environmental conditions, chemical compositions, and occupant activities. Overall, the proposed study’s significance lies in providing insights and knowledge that can lead to recommendations and guidelines for practitioners in the health, environmental, facility management, and construction sectors. This will help to better manage indoor BEs, creating a desirable indoor microbial assemblage that improves the health and well-being of building occupants