Despite ursolic acid’s effectiveness in killing cancer cells and tolerability in recent clinical trials, its development as a therapeutic has been hindered by its low water solubility and inadequate bioavailability. Formulating ursolic acid micellar nanoparticles (U-NPs) encapsulated with a biodegradable polymer can significantly improve ursolic acid’s solubility, stability, and bioavailability in vitro. We have developed differently sized U-NPs coated with polyvinyl alcohol (PVA). The particle size, encapsulation efficiency, solubility, stability, and cytotoxicity of these U-NPs were characterized in several cancer cell lines. The results showed that, relative to DMSO-solubilised ursolic acid, U-NPs were more effective in killing cancer cells. To our knowledge, this study is the first to demonstrate the extent of the anti-cancer potency of U-NPs in combination with either tamoxifen, vincristine, or daunorubicin. Therefore, U-NPs offer an effective way to improve the anticancer efficiency of ursolic acid through a nanoparticle-drug delivery system.