Abstract Glioblastoma progression is spatially heterogeneous, but conventional imaging provides limited information about where subsequent tumor progression is likely to occur. We developed a directional magnetic resonance elastography (MRE) framework to test whether local post-treatment tumor–brain interface mechanics are associated with later spatial tumor progression. In a secondary analysis of a prospectively acquired glioblastoma cohort, wedge-level viscoelastic instability features were extracted from the first post-treatment MRE scan and related to novel tumor burden on the second post-treatment scan after excluding tumor already present on pretreatment or first post-treatment imaging. Nine patients had longitudinal imaging suitable for spatial comparison; six lesions showed net interval growth and were included in the primary wedge-level directional analysis, while three non-growing lesions were retained for descriptive comparison. In growing lesions, several directional mechanical features were descriptively associated with later novel tumor burden. In cluster-aware models accounting for within-patient dependence among wedges, mean Δtanδ showed the most consistent association with later wedge-level novel tumor fraction across mixed-effects and generalized estimating equation analyses. Associations were directionally stable across wedge-width sensitivity analyses. These findings provide proof of principle that post-treatment glioblastoma interface mechanics contain spatially resolved information related to where later tumor emergence occurs, supporting further validation of directional MRE as a framework for longitudinal mapping of progression geometry.