Biocompatible nanocomposites are hybrid organic–inorganic materials synthesized at the nanoscale, with the aim of improving their structural, functional and biological properties. They are about everything pertaining to new developments caused by diagnostic imaging. Nanocomposites can offer high mechanical strength, enhanced thermal and electrical properties, biocompatibility, as well as biodegradability at abandonment, and hence, they have a wide application field in the biomedical world, from tissue engineering to drug delivery and including bioimaging: In this chapter, synthesis, characterization, and application of biocompatible nanocomposites and their revolutionary promises in diagnostic imaging will be highlighted. The book also emphasizes some benefits associated with combining nanoparticles with polymers, particularly magnetic nanoparticles and quantum dots, in order to form advanced imaging agents. Promising nanocomposites have also gone ahead by assuring very good resolution and contrast in MRI, CT, and optical imaging modalities while offering possibilities for functionalized targeting and imaging with reduced cytotoxicity. In addition, organic polymer-inorganic hybrids broaden the horizon for finer imaging and therapeutic delivery. Some of the key challenges facing this domain today include the difficult concepts of biocompatibility and toxicity coupled with regulatory types of issues. Identification of such strategies might pave the way toward opening new avenues for clinical translation of these materials and pave the path toward future directions in this regard. This chapter describes the latest trends in innovative synthesis methods, including sol–gel processes, surface modification strategies, and functionalization, for improved drug delivery and imaging performance.