This paper discusses the groundwater vulnerability to pollution assessment for the Tirana–Ishmi alluvium aquifer, Albania. Economic activities, municipal wastewater discharged into rivers and groundwater overexploitation threaten to pollute the groundwater. Based on the aquifer characteristics and the available data, SINTACS was selected as the most realistic assessment model. The SINTACS parameters’ rates assigned to the aquifer’s characteristics (water table depth, infiltration, unsaturated zone, soil media, aquifer media, hydraulic conductivity, topography) were adapted to the local features, followed by GIS vulnerability mapping. Statistical analysis indicates that the unsaturated zone, hydraulic conductivity and aquifer media have the highest influence on groundwater vulnerability, whereas topography has the lowest influence. Validation through sensitivity analysis and nitrates content confirms the rational selection of the SINTACS model and the reliability of the study’s outputs. The most vulnerable areas to pollution are the recharge zones, followed by the highly urbanized Tirana City area, characterized by high levels of groundwater extraction rate and wastewater discharged into the rivers. The paper, being the first completed groundwater vulnerability assessment of the study area, could serve as a basis for a scientific–based groundwater management that should be considered in local territory planning.