Worldwide, development agencies have increased their investments in water supply and sanitation as a “powerful preventive medicine” to address infectious diseases. These interventions have focused on on-site technical interventions or social engineering approaches, emulating the result-based targets of the development goals. Against this backdrop, the study examines the following research question: What is the role of socio-cultural backgrounds, housing characteristics, and environmental hygiene practices in addressing water-transmitted diseases in the Tashkent province of Uzbekistan. In a country where public statistics and official maps are rarely accessible, and research is restrictive, the study carried out a household survey using open data kit (ODK) between July and October 2015 in Olmalik, an industrial district, and the Kibray urbanizing district in the province. The findings reveal that demographic factors, poor sanitation practices, housing characteristics, and social behaviors are key predictors of water-transmitted diseases in the two districts. In the industrial township, poor housing, larger household size, and poor excreta disposal habits increased the occurrence of diseases, while in urbanizing districts, higher household size, frequently eating out, and access to public taps significantly increased the occurrence of water-transmitted diseases. The study, which was carried out in a challenging institutional environment, highlights the need for Uzbekistan to focus their policies on environmental hygiene, demographic factors and social behavior as key interventions rather than merely on on-site drinking water and sanitation interventions.