Abstract Fossil fuels are the main non-renewable energy source that supply communities and cities of electric and motor energy. The high demand for fossil fuels decreases reserves, making it a political, social, and environmental issue. Hence, bioethanol, considered a renewable source compared to other sources of energy, has become a viable alternative. Its manufacturing starts with the previous treatment of agroindustrial or food waste, followed by a fermentation process in a bioreactor and a distillation process for purification. However, the bioethanol production cost is higher than gasoline production because it requires identifying proper operating conditions of the process, traditionally done through trial and error. Therefore, this work describes the simulation of the fermentation of bioethanol, by considering the fermentation thank as a closed thermodynamical system and identifying the optimum biomass feeding flow rate by using the Cuckoo Search algorithm. The identification of the optimal biomass feeding flow rate reduces the substrate consumption time up to 30%, with respect to the process in a batch operation.