Multidisciplinary and highly dynamic pHealth ecosystems according to the 5P Medicine paradigm require careful consideration of systems integration and interoperability within the domains knowledge space. The paper addresses the different aspects or levels of knowledge representation (KR) and management (KM) from cognitive theories (theories of knowledge) and modeling processes through notation up to processing, tooling and implementation. Thereby, it discusses language and grammar challenges and constraints, but also development process aspects and solutions, so demonstrating the limitation of data level considerations. Finally, it presents the ISO 23903 Interoperability and Integration Reference Architecture to solve the addressed problems and to correctly deploy existing standards and work products at any representational level including data models as well as data model integration and interoperability.