The evolution of ICT towards fast and robust data exchange promoted the blooming of successful technical and business concepts like cloud computing and virtualisation of enterprise assets. The escalation of service providers enabled the specialisation of enterprises (particularly SMEs) and the building of provider networks. This move from enterprise-concentric to service-dispersed strategies is leading to concerns about reaching and maintaining the interoperability between customer–provider pairs and their associated business networks. This is particularly true in the aerospace industry: a highly-competitive and demanding business supported by numerous applications, which may be general-purposed, specific, proprietary or open-sourced, all needing to be interoperable with the lowest impact on the business itself. This paper addresses the need for improving the sustainability of enterprise interoperability via the application of negotiations, with the objective of reducing the impact of changes and achieving the best solutions in the interoperability between the enterprises and their surrounding environment. It proposes a framework that features a negotiation mechanism for the management of changes towards the sustainability of the seamless business-to-business interactions, and describes its application on the real business case of the ESA-CDF space mission feasibility studies.