El-Kharga Oasis in Egypt relies primarily on the Nubian Sandstone Aquifer System as its main groundwater resource. This study assesses the quality and suitability of groundwater for multiple uses by analyzing 70 samples collected from various depths within the aquifer. Hydrochemical assessment was conducted using major ions along with a set of water quality indices, including total dissolved solids (TDS: 177-1502 mg l-1), sodium adsorption ratio (SAR: 0.63-5.46 meq l-1), residual sodium carbonate (RSC:-4.96-2.96 meq l-1), sodium percentage (Na%: 27.21-76.55%), soluble sodium percentage (SSP: 27.2-76.5%), Kelly's ratio (KR: 0.23-2.93), permeability index (PI: 32.7%-109.8%), and magnesium hazard (MH: 24.84%-64.48%). The results indicate that most major ion concentrations fall within acceptable limits, whereas Fe2+ and Mn2+ levels exceed the World Health Organization drinking water standards. Groundwater quality maps (WQMs) reveal that most samples are rated from excellent to permissible for drinking, livestock, and poultry, and range from highly to moderately suitable for irrigation. In addition, groundwater is appropriate for industrial purposes. Although overall groundwater quality is deemed suitable for various uses, particular attention should be given to improving its quality for irrigation and drinking. The findings highlight the importance of sustainable groundwater management strategies to safeguard public health, support agricultural productivity, and preserve environmental sustainability in El-Kharga Oasis.