Heat integration is one of the powerful tools to improve energy efficiency in industry. Originally it was developed for heat recovery at the process level and progressively extended to establish energy synergy between multiple plants regrouped in geographical areas called eco-industrial parks. Such site wide energy integration reduces the overall costs and further increases energy savings beyond what may be achieved by the process scale. Many methodologies and tools have been developed to identify the potential heat recovery and the optimal heat transfer network design as heat integration solution at both scales. However, integrated processes will become interdependent and the major interactions between these processes constitute a risk for designers, especially in the case of fluctuations in operating conditions. Thus, the operability issues are of vital importance to be considered in design methodologies and the flexibility assessment become an essential prerequisite of the heat transfer configuration in order to better take into account fluctuations and disturbances in the energy synergy networks. This work presents a nonlinear programming (NLP) model that tests the flexibility of a heat transfer network design between multiple processes subject to multiple scenarios of capacity and flow rates variation. The model assesses the capability of the heat integration structure to satisfy the heat exchange target and its ability to operate and to cope with varying operating conditions. A virtual case study is used to demonstrate this methodology and its applicability. (C) 2018 Elsevier Ltd. All rights reserved.