For the last 20 years, the field of industrial symbiosis (IS) has raised interest among academics and industries. IS consists of dissimilar entities sharing and valorising underutilised resources such as materials, energy, information, services, or technologies in the view of increasing the industrial system's circularity. Despite the benefits brought by IS, though, barriers hindering the full dissemination of IS remain. This paper presents a methodology developed in the framework of the H2020 European project EPOS that aims at removing some of the obstacles to the implementation of IS. The method follows a multidisciplinary approach that intents to trigger the interest of industry decision-makers and initiate efforts to optimise the use of energy and material resources through symbiosis. It is applied to an industrial cluster located in the Humber region of UK. The case study shows how the approach helped to identify several IS opportunities, how one particular high-potential symbiosis was further assessed, and how it led to the creation of a business case. It was estimated that the identified symbiosis could bring substantial economic (+2000 k€ pa), environmental (−4000 t of CO 2 eq. pa) and social (+7 years of healthy life) gains to the region.