Flood risk mapping is a key instrument for integrated flood risk management. The scope of this study was to create a methodology to assist in identifying flooding risk hotspots and potential flood-prone areas, thus providing a much quicker but reliable method for identifying areas with a high flooding risk. The methodology developed aimed to correlate the hydraulic simulation results obtained from a hydraulic analysis with topographic indexes that allowed the production of risk maps at the regional scale and for larger areas. Flooding susceptibility was assessed through the correlation of the hydraulic modelling results obtained from Hec-RAS with the Topographic Wetness Index (TWI), among other remote sensing indices (NDVI, NDWI, MNDWI, and fCover). The study area was set in northern Greece, in the region of Western Macedonia. The hydrological sub-basin has an area of 50.90 km² and is located in the catchment of Aiani. The first part of the study focused on integrating DTMs, remote sensing indexes, and geospatial data into a Geographic Information System (GIS) to generate high-quality cartographic information for flood risk analysis. The next phase was the implementation of the hydraulic analysis and modelling. Different flooding scenarios concerning different return periods were applied. The topographic indexes’ results were then calibrated, based on the hydraulic analysis outputs, in terms of i) thresholding and adjusting the acceptable value range, calibrating them based on the calculated inundation profiles for various return periods for a selected area, and ii) their correlation with other indices. The interpretation of the correlation between the TWI and the hydrological analysis as the flood risk potential offered a group of flood risk maps with distinct categorisations and classifications of risk areas (low to high), providing different flood zoning for different inundation areas according to different discharge flows.