Wadi El Assiuti represents a promising area for agricultural development and building new communities far from the overpopulated areas in the Nile Valley. An integrated approach of satellite-based data and geophysical data with borehole data was used for defining the area of interest, the sediment thickness, delineating the subsurface structures, and mapping the depth to the basement rocks, and defining the groundwater aquifers. Findings are: 1) Dramatic changes are detected in the anthropogenic activities at the entrance area of the wadi, making stress and heavy exploitation of the groundwater resources. However, the central and northeastern regions show no development; 2) Several structural trends in the directions of NNW, NW, NE, and E-W are cutting the basement rocks and sedimentary cover; 3) The depth to the basement rocks is increasing eastward from ~2.24 km to ~4.84 km; 4) Three groundwater-bearing reservoirs are represented by the shallow Quaternary, the fractured limestone, and the deep Nubian sandstone aquifers; 5) The deep-seated faults are affecting the area and rising groundwater from the deeper Nubian aquifer along its sub-vertical trend; and 6) The results are informative and used to define the suitable sites for water well drilling.