Partial nitritation (PN) coupled with the anaerobic ammonium oxidation (Anammox) process has improved ammonium removal in wastewater treatment plants (WWTPs). The operation conditions of this process, i.e., the dissolved oxygen (DO) and the influent ammonium and nitrite concentrations, drive the process to an equilibrium to suppress nitrite-oxidizing bacteria and achieve a proper nitrite over ammonium (NO2/NH4) ratio. This study aimed to implement a set of control strategies in a WWTP model BSM2-SHAMX, combining PN in a single reactor system for high-activity ammonia removal over nitrite (SHARON) to an Anammox reactor, using proportional–integrative–derivative (PID) control and model predictive control (MPC) in a cascade. For correct coupling, the PN should maintain an output NO2/NH4 ratio between 1 and 1.3, suitable for the Anammox process. In the cascade controller feedback loop, the primary control loop controls the NO2/NH4 ratio through the DO concentration from the secondary control loop, which guarantees better effluent nitrogen removal. The performance of the plant was assessed by evaluating the control strategies with different influent carbon/nitrogen (C/N) loadings. The study results showed that the MPC controllers provided better results, with an improvement of 36% in the operational cost compared to the base case with a cost around 26,000 EUR/d, and better nitrogen removal surpassing 90% removal, 10% more than the base case.