Nowadays, nano-platforms designed for drug delivery systems (DDSs) such as polymers, liposomes, and micelles have been demonstrated to be clinically efficient. The sustained drug release is one of the advantages of DDSs, especially polymer-based nanoparticles. The formulation could enhance the drug's durability, in which the biodegradable polymers are the most interesting building blocks of DDSs. Nano-carriers could circumvent many issues by localized drug delivery and release via certain internalization routes such as intracellular endocytosis paths and increasing biocompatibility. Polymeric nanoparticles and their nanocomposite are one of the most important classes of materials that can be used for the assembly of nanocarriers that can form complex, conjugated and encapsulated forms. The site-specific drug delivery may arise from the ability of nanocarriers to pass through the biological barrier, their specific interactions with receptors, and passive targeting. The better circulation, uptake, and stability along with targeting attributes lead to lesser side effects and damage to normal cells. Hence, in this review, the most recent achievements on polycaprolactone-based or -modified nanoparticles in drug delivery systems (DDSs) for 5-fluorouracil (5-FU) are presented.