Cancer Medicine published by John Wiley & Sons Ltd. BACKGROUND: For Glioblastoma (GBM), various prognostic nomograms have been proposed. This study aims to evaluate machine learning models to predict patients' overall survival (OS) and progression-free survival (PFS) on the basis of clinical, pathological, semantic MRI-based, and FET-PET/CT-derived information. Finally, the value of adding treatment features was evaluated. METHODS: One hundred and eighty-nine patients were retrospectively analyzed. We assessed clinical, pathological, and treatment information. The VASARI set of semantic imaging features was determined on MRIs. Metabolic information was retained from preoperative FET-PET/CT images. We generated multiple random survival forest prediction models on a patient training set and performed internal validation. Single feature class models were created including "clinical," "pathological," "MRI-based," and "FET-PET/CT-based" models, as well as combinations. Treatment features were combined with all other features. RESULTS: Of all single feature class models, the MRI-based model had the highest prediction performance on the validation set for OS (C-index: 0.61 [95% confidence interval: 0.51-0.72]) and PFS (C-index: 0.61 [0.50-0.72]). The combination of all features did increase performance above all single feature class models up to C-indices of 0.70 (0.59-0.84) and 0.68 (0.57-0.78) for OS and PFS, respectively. Adding treatment information further increased prognostic performance up to C-indices of 0.73 (0.62-0.84) and 0.71 (0.60-0.81) on the validation set for OS and PFS, respectively, allowing significant stratification of patient groups for OS. CONCLUSIONS: MRI-based features were the most relevant feature class for prognostic assessment. Combining clinical, pathological, and imaging information increased predictive power for OS and PFS. A further increase was achieved by adding treatment features.