Patient‐specific cancer therapies can evolve by vitalizing the mother tissue‐like cancer niche, cellular profile, genetic signature, and drug responsiveness. This evolution has enabled the elucidation of a key mechanism along with development of the mechanism‐driven therapy. After surgical treatment, glioblastoma (GBM) patients require prompt therapy within 14 days in a patient‐specific manner. Hence, this study approaches direct culture of GBM patient tissue (1 mm diameter) in a microchannel network chip. Cancer vasculature‐mimetic perfusion can support the preservation of the mother tissue‐like characteristic signatures and microenvironment. When temozolomide and radiation are administered within 1 day, the responsiveness of the tissue in the chip reflected the clinical outcomes, thereby overcoming the time‐consuming process of cell and organoid culture. When the tissue chip culture is continued, the intact GBM signature gets lost, and the outward migration of stem cells from the tissue origin increases, indicating a leaving‐home effect on the family dismantle. Nanovesicle production using GBM stem cells enables self‐chasing of the cells that escape the temozolomide effect owing to quiescence. The anti‐PTPRZ1 peptide display and temozolomide loading to nanovesicles awakes cancer stem cells from the quiescent stage to death. This study suggests a GBM clinic‐driven avatar platform and mechanism‐learned nanotherapy for translation. Glioblastoma niche and drug responsiveness are preserved by culturing patient tissues in microchannel chips. As cancer stem cells migrate from the tissue following channels, cancer RNA signature of the tissue disappear. Nanovesicles are produced using glioblastoma stem cells with temozolomide loading and stem cell targeting peptide display, which chases to have committed the suicide of cancer stem cells by awakening their quiescence.