La Réunion Island has been considered an attractive target for geothermal exploitation since the 1970s. However, to date, the island's geothermal resources are not being used. Here we use for the first time, a Geographic Information System (GIS) as a decision-making tool to target the most favorable zones for exploitation of moderate and high temperature geothermal resources. All data acquired since the 1970s (geology, geophysics, geochemistry) in addition to environmental constraints such as protection of the National Park that was recently classified as a UNESCO World Heritage Site, were analyzed using the weighted overlay method to delineate favorable areas for local geothermal exploration. Three thematic maps were constructed: geological and structural indicators, thermal indicators, and geophysical indicators. Cross-analysis of these maps highlights two zones that have high geothermal potential; six zones with unconfirmed geothermal potential; and two zones located within the National Park protected area and thus subject to stringent exploitation regulations. It appears that, while thermal anomalies exist in several areas, permeability of the geological formations is low or insufficient for traditional geothermal utilization. Future exploration phases should assess the feasibility of using enhanced geothermal system (EGS) technologies to obtain a satisfactory economic return.