The promising biomedical applications of graphene oxide (GO) have quickly catalyzed a generation of various GO-based functional composites with desirable nanostructures and composites to satisfy the specific biomedical applications of GO-based nanosystems. This comprehensive review summarizes and discusses the very recent developments in rational design, chemical fabrication and versatile biomedical applications of GO-based functional composites, including metal oxide-GO, metal-GO, fluorescent nanoparticles-GO, silica-GO, polymer-GO and other specific GO-based composite nanosystems. The integration of multi-components with GO is also discussed. Their versatile theranostic applications include diagnostic imaging-guided therapy (photothermal therapy, photodynamic therapy and chemotherapy), biosensing-based tumor detection, and synergistic therapy. The biocompatibility and biosafety of these promising GO-based nanocomposites are also briefly mentioned. Finally, the unresolved critical issues and challenges facing the design/fabrication/application of these unique GO-based functional nanocomposites are proposed to further promote their clinical translation. The unique multi-composition, nanostructure and unique theranostic performance of GO-based composites are highly expected to pave a new way for the development of highly efficient theranostic protocols/approaches for precise personalized biomedicine to benefit human health.