Glioblastoma (GBM) is the most aggressive and lethal form of brain tumor in human adults. Myeloid-lineage cells, including macrophages, microglia, myeloid-derived suppressor cells (MDSCs), and neutrophils, are the most frequent types of cell in the GBM tumor microenvironment (TME) that contribute to tumor progression. Emerging experimental evidence indicates that symbiotic interactions between cancer cells and myeloid cells are critical for tumor growth and immunotherapy resistance in GBM. In this review, we discuss the molecular mechanisms whereby cancer cells shape a myeloid cell-mediated immunosuppressive TME and, reciprocally, how such myeloid cells affect tumor progression and immunotherapy efficiency in GBM. Moreover, we highlight tumor-T cell symbiosis and summarize immunotherapeutic strategies intercepting this co-dependency in GBM.