eHealth and pHealth, instantiated, e.g., in telepathology solutions, have to meet advanced interoperability challenges. Technologically supported by pervasive computing and even autonomic computing, pHealth covers many domains, scientifically managed by specialized disciplines using their specific ontologies. Therefore, semantic interoperability has to advance from a communication protocol to knowledge coordination and sharing, deploying advanced system architectures. Based on long-term work of scientific institutions and SDOs dedicated to system architectures, an interoperability framework is presented, integrating existing, emerging and even future specifications and standards for comprehensive interoperability of health and social services. The methodology is proven in many health information systems implementation and standard developments projects.