This work focuses on developing a novel method to optimize the fabrication conditions of polyamide (PA) thin film composite (TFC) membranes using the multi-objective genetic algorithm II (MOGA-II) method. We used different fabrication conditions for formation of polyamide layer—trimesoyl chloride (TMC) concentration, reaction time (t), and curing temperature (Tc)—at different levels, and designed the experiment using the factorial design method. Three functions (polynomial, neural network, and radial basis) were used to generate the response surface model (RSM). The results showed that the radial basis predicted good results (R² = 1) and was selected to generate the RSM that was used as the solver for MOGA-II. The experimental results indicate that TMC concentration and t have the highest influence on water flux, while NaCl rejection is mainly affected by the TMC concentration, t, and Tc. Moreover, the TMC concentration controls the density of the PA, whereas t confers the PA layer thickness. In the optimization run, MOGA-II was used to determine optimal parametric conditions for maximizing water flux and NaCl rejection with constraints on the maximum acceptable levels of Na₂SO₄, MgSO₄, and MgCl₂ rejections. The optimized solutions were obtained for longer t, higher Tc, and different TMC concentration levels.