In this manuscript, a two-input two-output (TITO) control strategy for an exothermic continuous chemical reactor is presented. The control tasks of the continuous chemical reactor are related to temperature regulation by a standard proportional-integral (PI) controller. The selected set point increases reactor productivity due to the temperature effect and prevents potential thermal runaway, and the temperature increases until it reaches isothermal operating conditions. Then, an optimal controller is activated to increase the mass reactor productivity. The optimal control strategy is based on a Euler-Lagrange framework, in which the corresponding Lagrangian is based on the model equations of the reactor, and the optimal controller is coupled with an uncertainty estimator to infer the unknown terms required by the proposed controller. As a benchmark, a continuous stirred tank reactor (CSTR) with a Van de Vusse chemical reaction is considered as an application case study. Notably, the proposed methodology is generally applicable to any continuous stirred tank reactor. The results of numerical experiments verify the satisfactory performance of the proposed control strategy.