Immunotherapies represented by immune checkpoint inhibitors and CAR−T cell therapy have fundamentally transformed the cancer treatment landscape, yet they have repeatedly failed against the most lethal brain tumor, glioblastoma (GBM). Why does this "immunological storm" that has swept through oncology suddenly "extinguish" within the brain This review addresses a core scientific question: Are our current immunotherapy strategies trapped in a "whack−a−mole" predicament when confronting GBM's fortress−like immunosuppressive tumor microenvironment (TME), lacking a comprehensive battle blueprint Through critical examination of the root causes underlying current therapeutic failures, we identify fundamental limitations in drug delivery, target selection, and microenvironment remodeling across three critical dimensions. We propose that future breakthroughs must pivot from "single−target approaches" toward "multi−step, sequential TME holistic remodeling." This requires developing more intelligent delivery systems to "breach the fortress walls," implementing metabolic interventions and targeted suppressive cell elimination to "purify the battlefield," and ultimately "create winning opportunities" for immune effector cells. This review also explores how novel preclinical models and dynamic biomarkers can guide the implementation of this complex strategy, aiming to provide new insights and inspiration for igniting this "immunological desert" of GBM.