Semantic interoperability is the ability of computer systems to exchange data with unambiguous, shared meaning. Semantic interoperability is a requirement to enable machine computable logic, inferencing, knowledge discovery, and data federation between information systems.

Semantic interoperability is therefore concerned not just with the packaging of data (syntax), but the simultaneous transmission of the meaning with the data (semantics). This is accomplished by adding data about the data (metadata), linking each data element to a controlled, shared vocabulary. The meaning of the data is transmitted with the data itself, in one self-describing "information package" that is independent of any information system. It is this shared vocabulary, and its associated links to an ontology, which provides the foundation and capability of machine interpretation, inference, and logic.

Syntactic interoperability (see below) is a prerequisite for semantic interoperability. Syntactic interoperability refers to the packaging and transmission mechanisms for data. In healthcare, HL7 has been in use for over thirty years (which predates the internet and web technology), and uses the pipe character (|) as a data delimiter. The current internet standard for document markup is XML, which uses "< >" as a data delimiter. The data delimiters convey no meaning to the data other than to structure the data. Without a data dictionary to translate the contents of the delimiters, the data remains meaningless. While there are many attempts at creating data dictionaries and information models to associate with these data packaging mechanisms, none have been practical to implement. This has only perpetuated the ongoing "babelization" of data and inability to exchange data with meaning.

Since the introduction of the Semantic Web concept by Tim Berners-Lee in 1999, there has been growing interest and application of the W3C (World Wide Web Consortium) standards to provide web-scale semantic data exchange, federation, and inferencing capabilities.