Overexploitation, pollution, and anthropogenic activities threaten the sustainability of groundwater resources in the western Indo-Gangetic Basin. Meanwhile, distinguishing regions prone to contamination and understanding the natural and anthropogenic factors affecting groundwater quality is challenging due to the heterogeneous nature of aquifer systems and the lack of high-resolution spatial and temporal data on aquifer protective hydrogeological layers. This study presents a transdisciplinary robust approach combining regional electrical resistivity surveys, hydrogeological data, physicochemical analyses, and geospatial datasets to identify regions prone to contamination and understand the impacts of natural and anthropogenic factors on groundwater resources. This approach involves three key steps: evaluating the geohydraulic nature of aquifer protective hydrogeological layers, mapping the aquifer vulnerability index (AVI), and conducting comparative analyses of potentially vulnerable areas with groundwater quality index (GWQI) and hydrological factors. Firstly, model-based inversion of ID Vertical Electrical Sounding (VES) data provides insights into geoelectrical indices such as depth, thickness, apparent resistivity, longitudinal conductance, transverse resistance, and longitudinal resistivity of aquifer protective hydrogeological layers. Second, the Artificial Neural Network (ANN) model is used as a multilayer perceptron network to simulate hydraulic conductivity (K) using geoelectrical indices of aquifer protective hydrogeological layers. Subsequently, by considering ANN-derived K and VES-derived h of aquifer protective hydrogeological layers, the dynamic hydraulic resistance to the vertical flow of wastewater through the protective hydrogeological layers evaluated the index of the potentially vulnerable areas. Comparative analyses of potentially vulnerable areas with GWQI and hydrological factors (e.g., digital elevation model, soil, drainage density, lineament density, slope) enhance understanding regions prone to contaminants and land surface stress. Findings show that the ANN approach to simulate K, reducing effort with costs associated with slug testing is significant for AVI assessment. Furthermore, the geohydraulic characteristics, vulnerability indexing, and comparative analyses assist in identifying contamination-prone areas, improving groundwater resource protection and exploration activities.