The Romanian sector of the Danube Valley, located in the Southern and Eastern parts of the country, covers a large area where the life of resident communities is significantly shaped by the Danube River (1,075 km longIn Romania, heat-related phenomena (mainly drought) are affecting extended areas in the southern and south-eastern parts, where the study area lies. This study relies on the statistical data available at the lowest level of administrative territorial provided by the National Institute of Statistics and on the climate data provided by the National Meteorological Administration. The paper aims to develop a multi-criteria vulnerability assessment by identifying the levels of socio-economic vulnerability by computing a Heat Vulnerability Index (HVI) which takes into consideration a set of indicators grouped into three key components of vulnerability (Exposure, Sensitivity, and Adaptive Capacity). The current research is aimed to be useful for academics by improving the general understanding of heat-related vulnerability in an area under the influence of one of Europe's most important rivers, but also for local decision-makers and planners to further contribute to the local climate change mitigation and adaptation strategies.