ObjectiveFor realizing pervasive and ubiquitous health and social care services in a safe and high quality as well as efficient and effective way, health and social care systems have to meet new organizational, methodological, and technological paradigms. The resulting ecosystems are highly complex, highly distributed, and highly dynamic, following inter-organizational and even international approaches. Even though based on international, but domain-specific models and standards, achieving interoperability between such systems integrating multiple domains managed by multiple disciplines and their individually skilled actors is cumbersome. MethodsUsing the abstract presentation of any system by the universal type theory as well as universal logics and combining the resulting Barendregt Cube with parameters and the engineering approach of cognitive theories, systems theory, and good modeling best practices, this study argues for a generic reference architecture model moderating between the different perspectives and disciplines involved provide on that system. To represent architectural elements consistently, an aligned system of ontologies is used. ResultsThe system-oriented, architecture-centric, and ontology-based generic reference model allows for re-engineering the existing and emerging knowledge representations, models, and standards, also considering the real-world business processes and the related development process of supporting IT systems for the sake of comprehensive systems integration and interoperability. The solution enables the analysis, design, and implementation of dynamic, interoperable multi-domain systems without requesting continuous revision of existing specifications.