Increasing agricultural production is associated with serious contamination issues with different natural resources-principally groundwater resources, which are constantly used for irrigation in quasi-total agro-regions under arid and semi-arid climatic conditions. Different types of trace elements and heavy metals are measured at high levels in shallow aquifer water tables in agricultural lands. This nonpoint pollution represents a huge challenge, as it is often difficult to survey and remediate. In the agro-based region of SW Tunisia, the impacts of agricultural activities on natural resources have raised special concern about the availability of these resources in sufficient quantities and with suitable quality. Thus, the evolution of trace elements in deep groundwater resources [Complex Terminal (CT) and Continental Intercalaire (CI)] used for irrigation was assessed with respect to farming practices (irrigation rate, fertilizer application, etc.). Data from field survey and laboratory analyses proved that the concentrations of some trace elements, namely nitrate (NO3-), phosphate (PO42-), potassium (K+), bromine (Br), and fluorine (F-), in the sampled groundwater exceed the recommended values for irrigation waters, as they locally exceed 300 mg/L. According to the collected data, the contamination of these deep confined aquifers is spread across the study area and has been occurring continuously for more than 10 years. This pollution constrains the sustainable use of these resources and leads to numerous environmental issues. Furthermore, it brings serious health risks, as the contaminated deep aquifers are used for both agriculture and drinking purposes. The mismanagement of agricultural activities and farming practices has induced quality degradation of reservoirs at depths of more than 1500 and 2000 m, indicating that limited knowledge of the properties of the hydrogeological system is the main factor constraining a thorough understanding of the hydrodynamic behavior of the aquifers. Detailed, consistent, interdisciplinary characterization of these deep resources is required in order to implement promising management actions.