Urbanization, anthropogenic activities, and social determinants such as poverty and literacy rate greatly contribute to heat-related mortalities. The 2003 strong heat wave (Lucifer) in France resulted in catastrophic health consequences in the region that may be attributed to urbanization and other anthropogenic activities. Amiens is a medium-sized French city, where the average temperature has increased since the year 2000. In this study, we evaluated the Heat Vulnerability Index (HVI) in Amiens for extreme heat days recorded during three years (2018–2020). We used the principal component analysis (PCA) technique for fine-scale vulnerability mapping. The main types of considered data included (a) socioeconomic and demographic data, (b) air pollution, (c) land use and cover, (d) elderly heat illness, (e) social vulnerability, and (f) remote sensing data (land surface temperature (LST), mean elevation, normalized difference vegetation index (NDVI), and normalized difference water index (NDWI)). The output maps identified the hot zones through comprehensive GIS analysis. The resultant maps showed that high HVI exists in three typical areas: (1) areas with dense population and low vegetation, (2) areas with artificial surfaces (built-up areas), and (3) industrial zones. Low-HVI areas are in natural landscapes such as rivers and grasslands. Our analysis can be implemented in other cities to highlight areas at high risk of extreme heat and air pollution.