This study introduces a modified differential evolution approach (MoDE) for evaluating the optimal objective and parameter values of the friction stir welding (FSW) process of dissimilar materials: AA5083 and AA6061. The aim of this study is to investigate the ultimate (UTS), maximum hardness (MH), and minimum heat input (HI) of the weld zone. The controlled welding parameters were shoulder diameter, rotation speed, welding speed, tilt angle, pin type, reinforcement particle type, and tool pin movement direction. The D-optimal experimental design method was used to create the experiment and obtain the mathematical model for optimizing the targeted objectives. The optimal rotational speed, welding speed, shoulder diameter, tilt angle, pin-type, additive type, and tool pin movement are 1162.81 rpm, 52.73 mm/min, 21.17 mm, 2.37 degrees, straight cylindrical, silicon carbide, and straight movement direction, respectively. The optimal values for UTS, MH, and HI are 264.68 MPa, 105.56 HV, and 415.26 °C, respectively. The MoDE outcome exceeded particle swarm optimization (PSO), the original differential evolution algorithm (DE), and the D-optimal design (experiment) results. The MoDE provides better UTS, MH, and HI than other approaches by an average of 8.04%, 4.44%, and 2.44%, respectively. In particular, when comparing results produced by using various approaches, we discovered that the MoDE results are 7.45%, 4.45%, and 3.50% better than PSO, DE, and the experimental results, respectively. All methods were evaluated for their reliability by comparing the results of actual experiments to those predicted by theory, and we discovered that the MoDE yielded the smallest percentage difference between the two, at 1.49%, while PSO and DE yielded differences of 5.19% and 3.71%, respectively.