 Despite recent developments worldwide in the therapeutic care of osteosarcoma, OS, the ongoing challenges and overcoming limitations and side effects of chemotherapy drugs warrant new strategies to improve overall patient survival. Spurred by rapid progress in biomedicine, nanobiotechnology, and materials chemistry, chemotherapeutic drug delivery and treatment of OS has become possible in recent years. Here, we review recent advances in the design of drug delivery system, especially for chemotherapeutic drugs in OS, and discuss the relative merits and trials along with future therapeutic options. These advances may pave the way for novel therapies requisite for patients with OS. This article was authored by Cheng Lengchen, Sherdong Wang, Wan Wang, and others.