Osteosarcoma, a primary malignant bone tumor commonly found in adolescents, is highly aggressive, with a high rate of disability and mortality. It has a profound negative impact on both the physical and psychological well-being of patients. The standard treatment approach, comprising surgery and chemotherapy, has seen little improvement in patient outcomes over the past several decades. Once relapse or metastasis occurs, prognosis worsens significantly. Therefore, there is an urgent need to explore new therapeutic approaches. In recent years, the successful application of immunotherapy in certain cancers has demonstrated its potential in the field of cancer treatment. Macrophages are the predominant components of the immune microenvironment in osteosarcoma and represent critical targets for immunotherapy. Macrophages exhibit dual characteristics
while they play a key role in maintaining tumor-promoting properties within the microenvironment, such as inflammation, angiogenesis, and immune suppression, they also possess antitumor potential as part of the innate immune system. A deeper understanding of macrophages and their relationship with osteosarcoma is essential for the development of novel therapeutic strategies.