Abstract: Osteosarcoma (OS) is a common primary malignant bone tumor occurring predominantly in children and adolescents. The main treatments for OS are surgical resection and chemotherapy. Although overall survival rates have improved, progress has stalled in recent years, particularly in cases of recurrence and metastasis. The tumor microenvironment (TME) is closely related to tumor development, and macrophages are among the most abundant immune cells within the tumor environment. As a new target for tumor immunotherapy, macrophages have gained increasing attention due to their significant role in tumor progression. In this review, we explore the role of macrophages in the OS microenvironment and discuss their clinical significance and involvement in the occurrence and development of OS. Furthermore, we summarize the therapeutic strategies targeting macrophages for OS treatment.