Adhering to FAIR principles (findability, accessibility, interoperability, reusability) ensures sustainability and reliable exchange of data and metadata. Research communities need common infrastructures and information models to collect, store, manage and work with data and metadata. The German initiative NFDI4Health created a metadata schema and an infrastructure integrating existing platforms based on different information models and standards. To ensure system compatibility and enhance data integration possibilities, we mapped the Investigation-Study-Assay (ISA) model to Fast Healthcare Interoperability Resources (FHIR). We present the mapping in FHIR logical models, a resulting FHIR resources’ network and challenges that we encountered. Challenges mainly related to ISA’s genericness, and to different structures and datatypes used in ISA and FHIR. Mapping ISA to FHIR is feasible but requires further analyses of example data and adaptations to better specify target FHIR elements, and enable possible automatized conversions from ISA to FHIR.