Systems and methods for controlling a performance variable of an engine system are provided. An apparatus includes a response model circuit structured to apply a constraint to a response model that represents a relationship regarding a manipulated variable or a relationship between the performance variable and the manipulated variable. The apparatus further includes an optimization circuit structured to determine a target for the manipulated variable via the response model such that the target of the manipulated variable satisfies the constraint of the response model. The performance variable is indicative of performance of operation of the engine system and the manipulated variable is capable of affecting the performance variable. Operation of the engine system is adjusted based upon the target of the manipulated variable by controlling at least one of a fuel system or an air handling system of the engine system.