Purpose <p>Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. Its diffuse infiltration affects distant brain regions, including the contralesional hemisphere, where structural and functional changes often escape standard imaging. This study aims to link cortical and connectivity changes to survival and tumour proliferation.</p> Methods <p>Thirty-one patients with isocitrate dehydrogenase (IDH)-wildtype GBM underwent pre-surgical MRI. Cortical surface area and thickness were analyzed using the Desikan-Killiany atlas, and structural connectivity metrics were derived from diffusion tensor imaging (DTI) using graph-theory analysis. Forward stepwise linear regression assessed cortical and connectivity metrics in relation to survival and Ki-67 levels, adjusting for age and sex. False discovery rate corrections were applied.</p> Results <p>Contralesional cortical surface area in the isthmus-cingulate (<i>P</i> &lt; 0.001) and inferior-parietal lobule (<i>P</i> = 0.001) negatively correlated with survival, while larger areas in the pars triangularis (<i>P</i> &lt; 0.001) and fusiform gyrus (<i>P</i> = 0.004) showed positive associations. Betweenness centrality in the pars triangularis (<i>P</i> = 0.015) and cuneus (<i>P</i> = 0.005) correlated negatively with survival. Higher values of global efficiency (<i>P</i> = 0.043), transitivity (<i>P</i> = 0.023) and betweenness centrality of the superior occipital gyrus (<i>P</i> = 0.013), were associated with increased Ki-67 levels.</p> Conclusions <p>GBM induces cortical remodeling and altered connectivity in the contralesional hemisphere, reflecting neuroplastic compensation and tumor-related adaptations. These changes, while supporting functional recovery, may inadvertently promote tumor progression. These subtle connectivity and cortical surface metrics offer insights into GBM progression and hold potential for improving prognostic accuracy.</p>