Multi‐objective optimization of dimethyl oxalate (DMO) hydrogenation to produce ethylene glycol (EG) is performed for three problems with four different objectives: maximization of DMO conversion and minimization of energy cost for problem 1; maximization of productivity and minimization of energy cost for problem 2; maximization of productivity and minimization of side product for problem 3; minimization of bare module and energy cost for problem 4; maximization of productivity and minimization of bare module for problem 5, and maximization of productivity and minimization of bare module and energy cost for problem 6. Multi‐objective differential evolution with ranking‐based mutation operator is applied to tackle the optimization problem with ASPEN simulator as model‐based optimization for EG production. The plots of decision variables denote that the optimal solution is strongly dependent on temperature.