This chapter provides a background of waterborne thermosetting polyurethane composite synthesis, physico-chemical properties and their applications as coatings, adhesives and printing inks. The reinforcement of waterborne polyurethane dispersion (PUD) matrix with different inorganic nanofillers develops cross-linking networks and leads to their high modulus, strength, durability, and resistance towards weather and chemical attacks. Thereby, a brief survey on different functionalization methods of nanofillers for the development of advanced waterborne PUD thermosetting composites with specific properties, including shape memory, fire retardancy, corrosion resistance and antimicrobial activity, is given.