Osteosarcoma, a primary malignant bone tumor, predominantly affects children and young adults, with a high incidence during puberty. Early diagnosis is critical due to the rapid tumor growth. Neoadjuvant chemotherapy has improved outcomes slightly, but prognosis remains poor in South Asia. Socioeconomic challenges and limited access to advanced therapies hinder effective treatment in this region. Despite global advancements in chemotherapy and surgical techniques, outcomes in low- and middle-income countries remain suboptimal. This review highlights the epidemiological challenges, diagnostic obstacles, and treatment barriers faced in South Asia, emphasizing the need for more accessible therapeutic approaches and improved healthcare systems.