Water is at the core for achieving all 17 sustainable development goals (SDGs). The current study was performed for the appraisal and modeling of the vulnerability of regional aquifers to anthropogenic perturbations. Samples of water were examined to determine their physical and chemical properties. pH of groundwater varied from a value of 7.08 to a value of 8.46. Total dissolved solids (TDS) varied from 1048‒1580 mgL-1. Results revealed that 79% of Ca2+, 47.3 % of Mg2+, and 100% of Na+ and Cl‒ in water samples exceeded the standard permissible limits. The Aquifer Vulnerability Index (AVI) revealed that Neogene aquifer was categorized as high vulnerability to extremely high vulnerability class to risk of contamination. AVI Index method was also performed for the other major aquifers demonstrating that Dammam aquifer was categorized in the high vulnerability class, Er Radhuma and Aruma categorized as moderately vulnerable to contamination. This study demonstrated an integrated model to help investigate the vulnerability of regional aquifers and highlighted the need for continuous monitoring campaigns to investigate the effects of anthropogenic activities on aquifers to make timely and effective decisions