Advanced health and social services paradigms are supported by a comprehensive set of domains managed by different scientific disciplines. Interoperability has to evolve beyond information and communication technology (ICT) concerns, including the real world business domains and their processes, but also the individual context of all actors involved. So, the system must properly reflect the environment in front and around the computer as essential and even defining part of the health system. This paper introduces an ICT-independent system-theoretical, ontology-driven reference architecture model allowing the representation and harmonization of all domains involved including the transformation into an appropriate ICT design and implementation. The entire process is completely formalized and can therefore be fully automated.