Polyhedral oligomeric silsesquioxane (POSS) hybrid nanoparticles have been considered as one of the most favorable nano-reinforcements in the field of high-performance advanced hybrid composites used for high-tech applications. Therefore, researchers around the world have devoted more attention to study its well-defined multifunctional nanostructure, amenable functionalization, hybrid nature, and ease of processability. The introduction of POSS into polymer matrices enhances their thermal, mechanical, thermo-mechanical, dielectric, and morphological properties and also improves resistance to moisture, corrosion, oxidation, UV, and microbial organisms of resulting polymer nanocomposites. In this chapter, we describe the synthesis, characterization, and properties of various POSS nanoparticles including nonreactive, monofunctional, bifunctional, and multifunctional POSS derivatives.