One powerful way to improve energy efficiency in industry is through Heat Integration. The heat recovery application was extended to multiple processes in eco-industrial parks offering important energy efficiency improvements. Many methodologies have been developed to apply the side wide heat integration concept; it sets energy target for the heat exchange that can be achieved between the processes using a common utility system. Nerveless, deviations of operating parameters such as supply and target temperatures and flow rates from nominal values are an everyday reality, thus the assumption of specific operation modes of the sites in heat integration methodologies that have been developed is not sufficient to justify investments especially with all the interactions between the interdependent processes that can occur. Consequently, any suggested design of heat transport network must be able to operate in all encountered operating conditions. The present work uses a mathematical optimization approach based on a mixed integer linear programming MILP model for the synthesis of heat exchange and transport networks between multiple processes covering energetic and economic aspects and employing the multi period approach to represent the variability of streams. The methodology is illustrated by applications to two case studies of virtual eco-industrial parks. (C) 2019 Elsevier Ltd. All rights reserved.