In this paper, we present an approach for building medical domain ontology as a foundation for knowledge-centric decision support. The knowledge acquisition phase is based on heterogeneous data sources including textual corpora, practice guidelines, databases, terminological sources as well as existing ontologies and medical Standards. Beyond a knowledge modelization process, we propose a meta-conceptualization and a formalization phase constituting a Medical Core-Ontology established at a high-level of abstraction and guiding the operationalization and exploitation phase. The operationalization process instantiates a referential medical domain ontology and integrates it into a knowledge-based system allowing knowledge reasoning and inference and thus, preparing the basis for a medical decision support.