Temozolomide chemotherapy triggers glioblastoma cells into senescence through two distinct morphological pathways: early extension-rich cells (E-state) and later flattened cells (F-state) that can interconvert. F-state cells show progressive nuclear enlargement, extended survival, and paradoxically lower p16 levels despite appearing more permanently senescent. Critically, these morphotypes exhibit different survival mechanisms—F-state cells have reduced autophagy and anti-apoptotic Bcl-2 proteins, while E-state cells are preferentially eliminated by dasatinib senolytic therapy. This morphological plasticity represents a significant challenge for glioblastoma treatment, as senescent cancer cells typically fuel tumor recurrence and treatment resistance. The finding that different senescent cell states have distinct vulnerabilities opens new therapeutic avenues. Rather than blanket senolytic approaches, targeting specific morphotypes could be more effective. The interconversion between states suggests senescent glioblastoma cells maintain dangerous adaptability, potentially explaining why these aggressive brain tumors frequently recur after chemotherapy. This granular understanding of senescence heterogeneity could inform more precise timing and selection of senolytic drugs in combination with standard chemotherapy.