Objective: This study aimed to evaluate the correlation between temporal muscle thickness (TMT) and Prognostic Nutritional Index (PNI) with disease progression in patients with high-grade brain tumors. Material and Methods: TMT was measured from the magnetic resonance images of 70 patients at the time of diagnosis. The TMT difference value was calculated by subtracting the post-treatment TMT value from the pre-treatment TMT value. The PNI value was determined by analyzing the complete blood count and biochemical parameter values at the time of diagnosis. Kaplan-Meier analyses and stepwise multivariate Cox regression analyses were used to assess the correlation of TMT and PNI with overall survival (OS) and progression-free survival (PFS). Results: Low PNI and high TMT difference values were correlated with the OS. OS analysis revealed that the mortality risk of patients with PNI<48.2 and TMT difference ≥0.9 was 3.4-fold higher than that of patients with PNI≥48.2 and TMT difference <0.9. Similarly, PFS analysis revealed that the mortality risk of patients with PNI<48.2 and TMT difference ≥0.9 was 2.3-fold higher than that in patients with PNI≥48.2 and TMT difference <0.9. Conclusion: This study demonstrated the prognostic value of TMT and PNI in high-grade brain tumors and revealed the enhanced power of the combination of TMT and PNI in predicting mortality. Thus, regular monitoring of TMT and PNI during the treatment can provide valuable insights into patient prognosis and aid in developing effective, individualized treatment strategies and consequently improving the OS outcomes and quality of life of patients.