The MSCs, CAFs, and CSCs secrete exosomes containing specific proteins and genetic materials to promote the proliferation, metastasis, and invasion of osteosarcoma. Meanwhile, osteosarcoma cells generate exosomes targeting specific cells to promote angiogenesis, osteoclastogenesis, and immunomodulation of the supporting cells. Osteosarcoma promotes drug resistance, proliferation, and metastasis through exosome secretion. (Created in Biorender.com)