Internally staged design (ISD) was introduced as a method to lower front reverse osmosis (RO) element fluxes, yielding operational benefits. Systematic selection of the best ISD combinations has not been conducted as it is dependent on operating conditions (i.e., RO recovery and average flux). This study aimed to optimize seawater reverse osmosis (SWRO) operations using ISD for better product water quality and energy efficiency. A total of 36 ISD combinations were configured with three commercial SWRO membranes and systematically examined under varying operating conditions which were simulations of typical SWRO operation. A Pareto-optimal front, a non-dominated feasible solution set, was created to understand the tradeoff relationship between permeate quality and specific energy consumption while considering all parameters. The Pareto-optimal front was classified into five phases, and an analysis of phase changes provided optimal parameter settings for SWRO operation. However, the occurrence of colloidal fouling altered optimal ISD combinations on the Pareto-optimal front. Particularly, when SWRO membranes were fouled at high-recovery and -flux conditions, ISD combinations employing three different membrane types exhibited superior performance in terms of energy efficiency. With these results, the best SWRO operation was suggested depending on its performance requirements, and the advantages of ISD were further delineated.