Prussian blue nanoparticles (PBNPs) are a unique class of nanomaterials that offer exceptional stability, biosafety, and biocompatibility. The synthesis, characteristics, and prospective implications of PBNPs and other cyanide-bridged coordination polymers have recently been studied at the nanoscale. The PBNPs offer extreme flexibility in that they can be synthesized in different types of nanostructures, such as spherical, core shells, cubes, and other structures by employing relatively easy methods with fine tunability. In addition, novel surface functionalization strategies act as precursors to develop techniques that find applications in drug delivery, im-aging and sensing, among several others. The current review aims to analyze and summarize the most promising techniques for PBNP synthesis, strategies for surface engineering, recent biological applications, and future prospects. Surface-engineered PBNPs are envisaged to have a substantial impact not just in bio-medicine but also in other domains like energy storage, water decontamination, recycling, and waste management. This review provides an in-depth analysis of the potential of PBNPs as key components in diagnostics, therapeutics, and its implications for further use.