For a separation system producing multicomponent products, stream splitting besides stream bypassing has long been recognized as a technique that always reduces total mass load (TML) and should always be preferred over sequential processing. Nevertheless, our preliminary analysis has indicated that stream splitting can increase TML under certain circumstances which, in turn, may increase the cost of the system; furthermore, even when stream splitting reduces TML, it may increase the mass load of one or more difficult separations and increase the cost of the system. An exhaustive parametric study of a class of relatively simple problems is performed in this work to reveal the impact of stream splitting on the sequencing of separation systems. Some significant observations have been made, and some guidelines have been established for evolutionarily improving separation system sequencing involving stream splitting.