This work aims to present a design for optimal operation of mass exchange networks (MENs) with minimum total annual cost (TAC) and optimal split-range control. The proposed strategy consists of five main steps. First, MENs are formulated as mixed-integer nonlinear programming (MINLP) with minimized TAC. Second, a network flexibility test is performed to ensure feasibility for a large number of uncertain parameters that are generated randomly within the operating ranges. Next, parametric programming is used to find the active constraint regions, and integer linear programming (ILP) is used to formulate an optimal split-range control structure. Then, the optimal operations of the control structure are verified with the preliminary dynamic behaviors. Finally, the common equipment design data are presented. The validation of the proposed method of designing an optimal split-range control structure for MEN is performed by three case studies from El-Halwagi and Manousiouthakis's work (1989, 1990). The results do not guarantee global optimization, but are checked through flexibility and dynamics tests. They demonstrate that the obtained control structures can keep all mass fraction targets at the desired values, even with the saturation of some manipulated variables when MENs are disturbed by reductions of 10, 20, and 30% of the mass fractions of rich streams and lean streams.