Real-time optimization (RTO) is the lowest level in the decision-making process for operating chemical processes at which economics is directly taken into consideration. This work presents a systematic methodology for incorporating decisions pertinent to the structure and functionality of the regulatory control system (RCS) at the real-time optimization level. The proposed formulation consists of a set of linear constraints that determines the set of manipulated and controlled variables and the steady-state operating policy that minimizes the effects of disturbances on process economics. The methodology is applied to two case studies, including an evaporator process and a fluid catalytic cracking process. The results demonstrate that the methodology can be used to decrease the sensitivity of process economics to disturbances and to operate processes in a near optimal way with less frequent RTO executions.