This document has been developed by the Interoperability Task Force of the EOSC Executive Board FAIR Working Group, with participation from the Architecture WG. Achieving interoperability within EOSC is essential in order for the federation of services that will compose EOSC to provide added value for service users. In the context of the FAIR principles, interoperability is discussed in relation to the fact that “research data usually need to be integrated with other data; in addition, the data need to interoperate with applications or workflows for analysis, storage, and processing”. Our view on interoperability does not only consider data but also the many other research artefacts that may be used in the context of research activity, such as software code, scientific workflows, laboratory protocols, open hardware designs, etc. It also considers the need to make services and e-infrastructures as interoperable as possible. This document identifies the general principles that should drive the creation of the EOSC Interoperability Framework (EOSC IF), and organises them into the four layers that are commonly considered in other interoperability frameworks (e.g., the European Interoperability Framework - EIF): technical, semantic, organisational and legal interoperability. For each of these layers, a catalogue of problems and needs, as well as challenges and high-level recommendations have been proposed, which should be considered in the further development and implementation of the EOSC IF components. Such requirements and recommendations have been developed after an extensive review of related literature as well as by running interviews with stakeholders from ERICs (European Research Infrastructure Consortia), ESFRI (European Strategy Forum on Research Infrastructures) projects, service providers and research communities. Some examples of such requirements are: “every semantic artefact that is being maintained in EOSC must have sufficient associated documentation, with clear examples of usage and conceptual diagrams”, or “Coarse-grained and fine-grained dataset (and other research object) search tools need to be made available”, etc. The document finally contains a proposal for the management of FAIR Digital Objects in the context of EOSC and a reference architecture for the EOSC Interoperability Framework that is inspired by and extends the European Interoperability Reference Architecture (EIRA), identifying the main building blocks required.