A holistic methodological procedure to assess estuarine vulnerability within a spatio-temporal framework is presented. This approach quantifies the vulnerability of estuaries to point-source pollution considering the physical processes, the ecological features, and the social aspects related to the existing estuarine ecosystem services. Estuarine vulnerability is referred to those characteristics of an estuarine ecosystem that describe its potential to be harmed. Thus, vulnerability is presented as a combination of four parameters: Tidal Zoning (TZ), State of Conservation (SC), Susceptibility (SU), and Stratification (ST). TZ differs between intertidal and subtidal zones. SC is determined as a combination of Naturalness (NA) and Ecological Value (EV). NA is defined as the absence of physical anthropogenic modifications, and EV is described as the presence of singular flora and fauna. While SU is related to the flushing or cleaning capacity, ST accounts for the location of mixed, partially mixed/stratified and stratified areas in the estuary. Subsequently, categories, thresholds and assessment criteria for every parameter, and a composite index to integrate all of them, namely the Estuarine Vulnerability Index (EVI), are presented. EVI has been applied to the Suances Estuary (N Spain) to find out the optimal locations for hypothetical point discharges. The results obtained for the Suances Estuary confirm the suitability of the proposed methodology and its conceptual approach as a comprehensive and practical management tool to quantify and prioritize estuarine areas receiving point-source pollution.