Proper management of groundwater resources, as the main source of fresh water, is very important. Groundwater vulnerability assessment has been applied as a management tool for prioritizing the use of resources, controling the contaminant transfer and adopting cost-effective ways for aquifer management. This study has adopted a novel approach based on DRASTIC method, analytic hierarchy process (AHP), and genetic algorithm (GA) optimization method to assess the vulnerability of Shiraz aquifer. AHP was utilized to modify the rank of DRASTIC model’ s parameters and GA optimization model was used to optimize the weights of DRASTIC parameters based on hydro-geological characteristics and nitrate concentrations of the Shiraz aquifer. The main aim of the GA-AHP model was to maximize the DRASTIC index correlation with nitrate concentration. The vulnerability map of Shiraz plain was provided using geographic information system (GIS). The results suggested that the southern and southeastern areas of Shiraz plain were faced with very high and high classes of vulnerability, respectively. The Pearson correlation coefficient between the developed vulnerability index and the nitrate concentrations was estimated as 80%, which confirmed the accuracy of the vulnerability map of Shiraz plain.