Groundwater contamination in the Mediterranean Basin is a severe problem that has a significant impact on environmental ecosystems and human health. The unconventional uranium and the potentially toxic elements (PTEs) of phosphate rocks are the principal contaminants in the phosphate mining industry in Tunisia. Phosphogypsum (PG) results from the valorization of phosphate to fertilizers and phosphoric acid. PG stocks can be used in cement production, brick manufacturing, and soil amendments in desertic land, and can be resolved by using nanomaterial adsorbents. In the flat area of the study area, the increase in radioactivity (40K) is due to abusive fertilizer use. Geochemical and radiological analyses in the northern part of Tunisia and its karst shallow aquifer indicate significant contamination levels. The northern part exhibits moderate contamination, whereas the karst shallow aquifer shows higher contamination levels, particularly with elevated nitrate concentrations. In the phosphate basin, both washing phosphate and phosphogypsum reveal high levels of radioactive elements, with the latter showing especially high concentrations of radium. The shallow aquifer in this region has moderate contamination levels, while the deep geothermal aquifer also shows noticeable contamination but to a lesser degree compared to the shallow aquifer. The shallow groundwater is characterized by a higher value of radioactivity than the groundwater due to the contamination impact from the phosphate industry and the cumulative radioactivity disintegration. Finally, the nanoparticles and the electrostatic adsorption can decrease the PTEs and radionuclides from the contaminated water in the study area. Moreover, other key issues for advancing research on groundwater contamination are proposed in this study. It is time to valorize this PG and the other mines of (Fe, Pb, and Zn) in the socioeconomic sector in Tunisia and to minimize the environmental impact of the industrial sector’s extraction on groundwater and human health in the study area.