This paper presents a targeting strategy to solve the heat load distribution (HLD) problem for large-scale plant by dividing the system into sub-systems while considering the heat transfer opportunities between them. The methodology is based on a sequential approach. The optimal flow rates of utilities are first defined using a Mixed Integer Linear Programming (MILP) model. The site is then divided into the subsystems where the overall interaction is resumed into a pair of virtual hot and cold stream with nonlinear T-H profile. The HLD problem is solved between these subsystems in a sequential procedure by considering a MILP model between these virtual representative streams, while each time one of the sub-systems is switched from virtual streams to the real ones. The main advantages are to reduce the size of the HLD problem and to find a feasible solution which is compatible with the minimum energy requirement (MER) objective. The potential of direct heat recovery between sub-systems are considered and the method can be practically adopted to consider the restricted matches between sub-systems as well. This methodology has been currently applied on a real site scale process integration industrial example and in this paper its application is illustrated through a case study with 23 streams.