Traditionally, design and control issues have been addressed separately at different stages in the life cycle of a chemical plant. The process parameters are often selected in an ad hoc fashion during the design stage, and some of them later become the nominal set-point conditions in actual plant operation. The uncertain online disturbances associated with each set of operating conditions usually vary within a specific range centered at the nominal value. Because these arbitrarily chosen parameter values do not always result in the highest level of operational flexibility, it is thus desirable to develop a systematic method to optimally stipulate the nominal operating conditions of an existing process for maximum flexibility. The well-recognized flexibility index model is used in this work to evaluate system resiliency based on fixed nominal conditions, and a direct search method (differential evolution) is performed accordingly to identify the best candidates. Two examples are presented in this article to demonstrate the impacts of nominal settings and the effectiveness of the proposed optimization approach.