Groundwater constitutes a main source of drinking water and irrigation in regions with arid and semi-arid climates. In the Tlemcen region (North-West Algeria), resource accessibility has become a major problem following current climatic disturbances and socio-economic development which hamper the stability of resources on a regional scale. The present work was carried out on the karst aquifers of Tlemcen Mountains. The aim was to test the hydrogeological prospecting method for the borehole implantations by the use of water potential spatialization in the aforementioned aquifers. This concerns the assessment of the underground water potential by an integrated approach involving the association of remote sensing techniques, geographic information systems (GIS), and multi-criteria decision analysis (MCDA). Sixty groundwater boreholes were selected in the karst and nine parameters classified into 3 criteria (availability, accessibility and water exploitability have been integrated. They concern the slope (%), effective infiltration (mm), drainage density (km km−2), fracturing density (Km km−2), alteration thickness (m), total depth (m), success index (%), static level (m), and operating flow rate (m3 h−1). The Tlemcen Mountains delimited in this work over a drained area of 2838.78 km2, have an altimetric variation between 374 and 1830 m, with a dominance of high altitudes (800 to 1200 m). Slopes vary from 0 to 64%. The drainage network in this area has a dentritic shape and an average drainage density of 0.94 km km−2. The study area has an availability represented by a unique value. This availability could be explained by low slopes and high fracturing densities (1.95–2.37 km km−2), which are two parameters likely to favor the recharge of aquifers. The accessibility and water exploitability criteria are dominated by poor and good classes, covering 75% of the study area. These two classes located in the Northeast, are characterized by fairly deep well (>98 m) and fairly high success rates, revealing a strong exploitation rate (>7.2 m3 h−1), thus favoring an exploitability of groundwater. The most favorable areas for well implantations are located in the extreme Northeast, in the surrounding of Ouled Mimoun city and in the Northwestern part of Tlemcen city. They correspond to the discharge areas of the fairly large flow aquifers. However, areas with poor potential are located in Sebdou region, South of Tlemcen Mountains, represented by old and recent Quaternary-age alluvium (Holocene).