Maximizing safe resection in neuro-oncology has become paramount to improving patient survival and outcomes. Laser interstitial thermal therapy (LITT) offers similar survival benefits to traditional resection, alongside shorter hospital stays and faster recovery times. The extent of ablation (EOA) achieved using LITT is linked to patient outcomes, with greater EOA correlating with improved outcomes. However, the preoperative predictors for achieving supramaximal ablation (EOA ≥ 100%) are not well understood. By leveraging machine learning (ML) techniques, this study aimed to identify these predictors to enhance patient selection and therefore outcomes. The objective was to explore preoperative predictors for supramaximal EOA using ML in patients with glioblastoma. A retrospective study was conducted on the medical records of 254 patients undergoing LITT from 2013 to 2023 at a single tertiary center. Cohort criteria included age ≥ 18 years, diagnosis of glioblastoma, single-trajectory ablation, and a complete dataset. The study assessed preoperative clinical and radiographic factors, using EOA ≥ 100% as the endpoint. Five ML models were used: logistic regression, random forest (RF), gradient boosting, Gaussian naive Bayes, and support vector machine. Training and testing cohorts were subsequently assessed across ML models with fivefold cross-validation. Models were optimized using hyperparameter tuning. Performance was primarily quantified using the area under the curve (AUC) of the receiver operating characteristic curve. The final cohort consisted of 72 patients. Among the ML models, RF achieved the highest AUC (mean ± SD 0.94 ± 0.06). The leading models identified that lower preoperative volume, history of prior radiation therapy, history of prior craniotomy, preoperative neurological deficits, history of preoperative seizures, and distance from intracranial heat sinks were predictive of successful ablations in patients. Additionally, RF had the best mean metrics: accuracy 0.88, precision 0.87, specificity 0.87, and sensitivity 0.89. This is the first study to investigate the role of ML for optimizing ablation volumes in LITT. These ML models suggest that low preoperative volumes, previous craniotomy, previous radiation therapy, no previous neurological deficits, larger catheter-heat sink distance, and the presence of preoperative seizures are important prognostic factors for predicting successful supramaximal ablations with LITT.