Background: Glioblastoma multiforme (GBM) poses a significant health challenge as the most common primary malignancy of the adult central nervous system. Gender and age-related differences in GBM influence prognosis and treatment complexities. This multicenter retrospective study explores gender and age disparities in GBM patients, investigating their impact on occurrence and survival outcomes. Methods: This STROBE-compliant retrospective study involved GBM patients who received medical care in Guilan Province, Iran. Patients’ data, including age, gender, tumor location, and histopathological diagnosis date, was collected from medical records. Results: In a cohort of 164 GBM patients, the average age was 54 years, with higher prevalence in men (59.8%) as well as patients ≤60 years (64.6%). The tumor sites exhibited overlapping features in 68% of cases, with the frontal and temporal lobes being the most prevalent specific locations. The mean survival was 12.88 ± 14.14 months, one-year survival of 45%, with women showing higher one-year survival (60% vs. 40%) and longer mean survival (16.14 ± 17.35 vs. 10.75 ± 11.15 months). Patients ≤60 years had higher one-year survival (75% vs. 35%). In subgroup analysis, women had significantly higher survival rates in patients ≤60 years. However, among patients over 60, women exhibited a more significant reduction in survival rates, and no statistically significant difference was observed between males and females in this age group. Discussion: While the biological mechanisms behind gender disparities in GBM remain unclear, studies suggest the potential involvement of sex hormones. Age-related differences, in line with the prior research, highlight the complexity of managing older GBM patients. Conclusion: This study underscores age and gender disparities in GBM occurrence and prognosis, emphasizing the necessity for further investigations and innovative approaches to address the potential pathogenesis.