It is paramount to optimize the performance of a chemical process in order to maximize its yield and productivity and to minimize the production cost and the environmental impact. The various objectives in optimization are often in conflict, and one must determine the best compromise solution usually using a representative model of the process. However, solving first-principle models can be a computationally intensive problem, thus making model-based multi-objective optimization (MOO) a time-consuming task. In this work, a methodology to perform the multi-objective optimization for a two-reactor system for the production of acrylic acid, using artificial neural networks (ANNs) as meta-models, is proposed in an effort to reduce the computational time required to circumscribe the Pareto domain. The performance of the meta-model confirmed good agreement between the experimental data and the model-predicted values of the existent relationships between the eight decision variables and the nine performance criteria of the process. Once the meta-model was built, the Pareto domain was circumscribed based on a genetic algorithm (GA) and ranked with the net flow method (NFM). Using the ANN surrogate model, the optimization time decreased by a factor of 15.5.