Cities face rapid changes leading to increasing inequalities and emerging public health issues that require cost-effective interventions. The urban exposome framework constitutes a novel approach in tackling city-wide challenges, such as those of drinking water quality and quality of life. In this proof-of-concept study, we presented part of the urban exposome of Limassol (Cyprus) focusing on chemical and microbial drinking water quality parameters and their association with urban neighborhood indicators. A perceptions study and an urban population study was conducted. We mapped the water quality parameters and participants’ opinions on city life (i.e. neighborhood life, health care and green space access) using quarters (small administrative areas) as the reference unit of the city. In an exploratory environment-wide association study analysis, we used all variables (questionnaire responses and water quality metrics) to describe correlations between them accounting, also, for self-reported health status. Overall, urban drinking-water quality using conventional indicators of chemical (disinfection byproducts-trihalomethanes) and microbial (coliforms, E. coli, and Enterococci) quality did not raise particular concerns. The general health and chronic health status of the urban participants were significantly (all >FDR corrected p value of 0.1) associated with different health conditions such as hypertension and asthma, or having financial issues in access to dental care. Additionally, correlations between trihalomethanes and participant characteristics (e.g. household cleaning, drinking water habits) were documented. This proof-of-concept study showed the potential of using integrative approaches to develop urban exposomic profiles and identifying within-city differentiated environmental and health indicators. The characterization of the urban exposome of Limassol will be expanded via the inclusion of biomonitoring tools and untargeted metabolomics platforms.