Remarkable advancements in material technologies have facilitated the use of many new materials in diverse applications. Among many new hybrid biomaterials, polymer nanocomposites have brought about a revolution especially because of their flexible functionalities and related advantageous properties (e.g., good strength, large surface area to volume ratio, large flame retardancy, high elastic modulus, and enhanced density). These nanocomposites have been successfully incorporated into diverse fields of applications such as drug delivery, tissue engineering, gene therapy, food preservation, biosensing, and bioimaging. As these nanocomposites permit the combination between unusual properties (e.g., thermo-mechanical, optoelectronic, and magnetic properties) and enhanced flexibility (e.g., in structural design), they appear to be more promising than other nanomaterials or conventional materials in many respects. Thus, the major focus of this review is to give a comprehensive overview of polymer nanocomposites along with their synthesis routes, surface treatment strategies, and applications in the healthcare sector (e.g., drug delivery, 3D bio-implant, bioimaging, food processing, and other biomedical applications). Our discussion also highlights future directions for this emerging field of research.