Karst is a peculiar natural landscape arising from high rock solubility and well-developed underground solutional channel porosity. It is unique for its surface relief (exokarst) and subsurface drainage, including cave systems (endokarst). In Portugal, karst areas mainly consist of marginal or low-density territories with great fragility and vulnerability and great geo-environmental richness that merits better policies and practices regarding their geo-conservation. Endokarst potential assessments can provide decision-makers and local authorities insight into present and future territorial management and planning. In this context, the main objective of this study was to produce a cartographic model to identify areas with a greater probability of containing karstic caves—i.e., a greater endokarst potential—in the northern sector of the Santo António Plateau (Estremadura Limestone Massif, Central Portugal). Geological, topographic, hydrogeological, and land cover data were collected, processed, and integrated into a spatial database using a Geographic Information System. The locations of known cave entrances in the study area were also identified from local public institutions and speleological team records. Subsequently, four conditioning factors were extracted from the data: lithostratigraphic units, fracture density, relief energy, and land cover. Using a multi-criteria decision-making analysis, each previously chosen conditioning factor and its respective classes were weighted using an analytic hierarchy process. The locations of known cave entrances served to evaluate the cartographic model built, with results showing an agreement of 81.9%. This prototype of the endokarst potential map for the study area may be used for strategic and operational environmental planning (at least on a local scale) to assist decision-makers, competent authorities, and local speleological teams. Its application may promote a more accurate and thoughtful definition of areas to be investigated, substantially reducing the time and costs associated with field prospecting.