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In this paper, we determine the groundwater vulnerability of the Iberian Peninsula on the spatial scale. Aquifers, infiltration map, water availability, pollution load index, and nitrate (NO3) data have been analyzed as independent factors and inserted into the “New Implemented Spatial-Temporal On Regions–Groundwater Vulnerability Index” (NISTOR-GWV index) model in the Geographical Information Systems platform in order to generate the groundwater vulnerability map of the Iberian Peninsula. The new approach, called the NISTOR-GWV index, was applied on current (2011–40: 2020s) and future periods (2041–70: 2050s). During the 2020s, high and very high vulnerability of groundwater are depicted in the Ebro River Basin, in the Tejo Valley, in the Baetic Depression, and in the Meseta Central. The vulnerability map indicates larger areas of high vulnerability class during the 2050s. The future scenarios show a significant decrement in the areas with low and very low vulnerability classes (scenario B2) in comparison with the current period, while the areas with the high and very high vulnerability increased for the 2050s (scenario B1). These results would seem to show that climate change and land cover modifications negatively affect the groundwater resources, mostly at the spatial scale. The most important implications to protect the aquifers could be addressed to the agriculture and environmental management planning. A good planning of water consumption, agricultural and irrigation water use in Spain and Portugal may lead to a reduction of climate impact on groundwater.