Glioma is the most common primary malignant tumor of the central nervous system in adults, characterized by high mortality, low cure rate and high recurrence rate. Among gliomas, glioblastoma multiforme (GBM) is the most malignant subtype. Currently, the standard treatment for patients with GBM is maximum surgical excision combined with radiotherapy and chemotherapy. But only a small percentage of patients benefit from this standard treatment. The tumor microenvironment plays an important role in the occurrence and development of most tumors. It is primarily composed of tumor cells, peripheral blood vessels, extracellular matrix, signaling molecules, stromal cells, and immune cells. The role of stromal cells in GBM has emerged as the focus of current research. The interaction among tumor, stromal, and immune cells within the tumor microenvironment can influence tumor development. Traditional research and drug therapy in glioma mainly focus on the tumor cells themselves, but recent studies have found that targeting stromal cells in the tumor microenvironment can also modulate tumor progression in GBM. Here, we review the influence of stromal cells in the tumor microenvironment of GBM on tumor cells and its related mechanism, as well as related molecular targets and signaling pathways, providing new ideas for the treatment and prognosis of GBM.