Nowadays, special attention is paid to the application of nanoparticles to improve the performance of Electrical Discharge Machining (EDM). In this paper, modeling and optimizing the process parameters of Nanopowder Mixed Electrical Discharge Machining (NPMEDM) is studied. In this study, the effect of aluminum oxide (Al₂O₃) and silicon oxide (SiO₂) nanoparticles on the deionized water dielectric is investigated simultaneously in the process of electrical discharge machining of Ti-6Al-4V alloy. After analyzing the parameters, the discharge current, concentration, pulse on time, and relative composition are considered as input factors. Response Surface Methodology (RSM) using Design-Expert software is employed for the design of the experiments, analysis of the results, and optimization of the parameters. The results show that the best surface morphology is obtained by machining with the addition of nanoparticles in the relative composition of 50%. In this percentage of the composition, the surface of the workpiece has the least value of crack and recast layer. In addition, the maximum value of the material removal rate (MRR) and minimum value of tool wear rate (TWR) can be achieved in the discharge current of 12 A, pulse on-time of 100 μs, and relative composition of 75% Al₂O₃ – 25% SiO₂.