Glioblastomas (GBM) are aggressive primary brain tumors that remain incurable, with a significant need for new treatment options. Most patients do not respond to cancer immunotherapy due to the immune-suppressive tumor microenvironment. GBM tumors are heavily infiltrated by macrophages, the predominant immune cells in the tumor, making them a key target for new therapeutic strategies. Our research aims to elucidate the origin, heterogeneity and functions of tumor-associated macrophages in GBM. We rely on single-cell and spatial omics profiling of human GBM tumors, supplemented with proof-of-concept studies in preclinical models. Our goal is to develop strategies for modulating macrophage functionality within tumors or to harness macrophages as vehicles for cell therapy, aiming to induce anti-tumor immunity.