Different control strategies have been investigated to improve nonlinear system operations. One such strategy is the use of nonlinear predictive controllers (NMPCs) based on machine learning models. These models, such as artificial neural networks (NN), support vector machines (SVMs), and neuro-fuzzy networks (NF), present satisfactory adaptability to the complexity of the processes. In this aspect, a comparative study of the models in the predictive control of a complex system, such as MIMO (multiple-input-multiple-output) process of the production process of cyclopentadiene, is of interest and is the aim of this work. In this aspect, we find, through simulations, that the NMPCs presented adequate performance, especially those based on an SVM, concerning the servo and regulatory problem scenarios, keeping the process at the optimum operating point, especially for unattainable setpoint. The instability in the use of the classical proportional-integral-derivative linear control is also shown.