Osteosarcoma (OS) is one of the most serious malignancies along with a high incidence in children and teenagers. Although the neoadjuvant chemotherapy of OS has made great progress and prolongs the five-year survival rates of patients to some extent, drugs are restrained from clinical application due to the unsatisfactory efficacy and severe side effects, especially for the systemic therapy through intravenous injection. The polymeric nanoparticles as anti-cancer drug nanocarriers make OS treatment more promising and effective. Specifically, various polymeric nanoparticles have been developed to overcome the difficulties in targeting delivery of drugs to OS tissue and/or cells through passive and/or active strategies. This review presents an overview on the development of polymeric nanoparticles for anti-cancer drug delivery in OS treatment, and briefly describes the challenge and opportunity for future development.