In this paper, the preparation of PPSU/PES/Nano silica composite ultrafiltration membranes by a combined vapor induced phase separation (VIPS) and non-solvent induced phase separation (NIPS) techniques were successfully investigated. For this purpose, the effect of VIPS time from 0 to 60s, the blending ratio of PPSU:PES from 0 to 100%, polymer concentration from 16 to 24wt.%, and SiO2 nanoparticles concentration from 0 to 5wt.% as an additive to dope solution on the performance and characteristics of ultrafiltration membranes were studied. As the number of parameters is high, the response surface methodology (RSM) was applied for designing the experiments for obtaining the optimum condition for the fabrication of a high flux ultrafiltration membrane. Liquid-liquid displacement porosimetry (LLDP), scanning electron microscope (SEM), pure water flux (PWF), and bovine serum albumin (BSA) retention were used for characterization of the fabricated membranes. The results are shown different trends for the effect of SiO2 nanoparticles concentration at the low and high polymer concentrations in dope solution. When the polymer concentration in the dope solution is low, the increase of SiO2 nanoparticles concentration resulted in lower fluxes, but at high polymer concentrations, the increase of the nanoparticles caused an increase in permeate flux. At optimum condition, the highest PWF of 76.65L/m².h (15.33L/m².h.bar), and a BSA retention of 82.01% was obtained.