<p>Telomerase activity is a surrogate marker of cancer cell biology, and predicting changes in telomerase activity in recurrent diseases could inform the therapeutic insights. Advanced multiparametric MRI (mpMRI) enables tumor characterization and may reveal imaging correlates of telomerase dynamics. We analyzed the tumor habitat and radiomics features derived from preoperative mpMRI obtained at both initial diagnosis and tumor recurrence in 20 patients with recurrent IDH-wildtype glioblastoma. These patients had previously been treated with the standard protocol of radiotherapy and temozolomide. The mpMRI included diffusion- and perfusion-weighted imaging. Longitudinal telomerase activity was measured by telomere repeat amplification protocol assay using tissues obtained from core area of tumor. High initial telomerase activity was associated with a larger volume of hypervascular cellular habitat (<i>p</i> = 0.025) within the enhancing region. Decreased telomerase activity was associated with a smaller volume of hypovascular cellular habitat within the non-enhancing region (<i>p</i> = 0.020), and with the 90th percentile of ADC within the tumor region (<i>p</i> = 0.036 on average). Habitat volume and telomerase activity were significantly associated with progression-free survival (<i>p</i> = 0.010 and <i>p</i> = 0.038, respectively). Additionally, changes in habitat volume were linked to alterations in enhancing tumor volume. Advanced mpMRI-derived habitat volumes and heterogeneity metrics represent promising non-invasive biomarkers of telomerase activity in recurrent glioblastoma, potentially supporting treatment stratification, and surgical planning.</p>