Multi-Plant Heat Integration is an established approach for improving energy efficiency in industrial clusters. Current studies mostly focus on this topic under a simple assumption that all plants are operating at a same and single period. In reality, processing plants may operate at multiple periods in which the operating conditions of each plant vary with time. Process stream parameters such as mass flow rates, supply and target temperatures may change over a specified range. So it is particularly necessary to design multi-period heat exchanger networks to improve the systems’ flexibility. While multi-period operation problem has been considered in some researches of heat exchanger network synthesis within a single plant, it is usually ignored in Multi-Plant Heat Integration studies. In this work, we propose a new methodology for Multi-Plant Heat Integration considering multi-period operations. The methodology employs a novel representative superstructure to cover all possible networks for Multi-Plant Heat Integration wherein the maximum area of a heat exchanger is required to achieve heat exchanging services in all periods. The problem was formulated as a mixed integer nonlinear programming (MINLP) problem. Trade-offs among utility cost, capital cost of heat exchangers, piping cost and pumping cost were fully investigated. An industrial case is employed to illustrate the effectiveness of proposed model.