This study aimed to improve the performance of a wastewater treatment plant (WWTP) simulated with Benchmark Model No. 2 (BSM2). To achieve this objective, three control strategies were implemented and tested. The first control strategy aimed to maintain the concentration of nitrate and nitrite nitrogen (S_NO) by controlling the external carbon flowrate (strategy A₁), and the second control strategy aimed to maintain the ammonia and ammonium nitrogen (S_NH) at a desired level with the use of a cascade controller (strategy A₂). The third strategy was applied to control the total suspended solids (TSS) (strategy A₃). Combinations of these strategies were considered (B₁, B₂, and B₃ strategies), as well as the use of all three together (strategy C₁). The control strategies presented in this paper were compared to the default control strategy of BSM2 to validate and identify the one that provided the best performance. The results revealed that the B₁ strategy was the most environmentally friendly, while C₁ obtained the highest overall performance. Several Monte Carlo simulations were performed for the validated control strategies, to identify the optimal setpoint values. For the C₁ strategy, a second method of optimization regarding polynomial interpolation was considered. The applied optimization methods provided the optimal reference values for the PI (proportional integral) controllers.