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Osteosarcoma and other solid tumor therapies remain urgent clinical challenges. Currently, treatment mainly relies on surgical resection. However, surgery often requires extensive removal of bone and surrounding tissues, which can easily lead to impaired limb function, affect patients' immune and metabolic functions, and increase the risk of recurrence. Smart nanomedicine offers new hope for the treatment of solid tumors. Nanoparticles can enable targeted drug delivery and personalized treatment, reduce damage to normal tissues, and help prevent dysfunction and disability. Postoperative adjuvant nanomedicines can help eliminate residual tumor cells, lower the recurrence rate, control distant metastasis, and improve survival rates. Additionally, nanoparticle-based immunotherapy has shown promising prospects. By integrating artificial intelligence and big data platforms, the development of smart nanomedicine systems can become more efficient, reliable, and tailored to the specific needs of osteosarcoma therapy. However, there are still biosafety, ethical, and regulatory challenges in clinical translation. In the future, it is necessary to further optimize the targeting and biocompatibility of nanocarriers, strengthen research on tumor metabolism, and improve regulatory systems to promote the clinical application and commercial development of multifunctional nanoparticles.