A dividing wall column (DWC) is a thermally coupled distillation system with a high energy efficiency that requires lower space and investment compared to the conventional column system. The design of a DWC involves a number of structural and process parameters that need to be optimized simultaneously to improve energetic and economic potential and reduce space requirement. We used response surface methodology (RSM) to optimize DWC nonlinearly and to figure out the effect of parameters and their interactions on energy consumption, product quality, and dimensions of a DWC. Results demonstrate that process variables have significant effects on the energy efficiency of a DWC as compared to the effect of structural variables. The optimum DWC parameters can be found by RSM with minimal simulation runs and the prediction results of RSM agree well with the rigorous simulation results.