Höchst Industrial Park (IPH) was founded in 1863. Over the years, a network of symbiotic relationships has developed between the companies in the park, the park, and the Rhine-Main region, resulting in the efficient use of resources. However, while this industrial symbiosis reduces greenhouse gas (GHG) emissions, a shift towards more sustainable energy and raw material supplies is required to meet climate goals. Options include renewable electricity, heat electrification, green hydrogen, carbon capture and utilisation, biomass, and recycling. Such a transformation is challenging because it requires the application of highly innovative technologies on a large scale, the cooperation of many public and private actors, a fast pace to achieve GHG reduction targets, and a high degree of structural complexity due to the need to adapt the infrastructure. This need must be managed amid considerable regulatory uncertainty, a lack of infrastructure for producing and transporting green hydrogen and electricity and increasing international competition between production sites. We analyse how established symbiotic relationships affect the transformation of an existing industrial park using the case of IPH and focus on the manufacturing companies at this site. In addition, we show how a defossilised energy supply in IPH could look and which new symbiotic relationships could develop. We also discuss the role of stakeholder management in achieving coordinated action.