Therapeutic hypothermia (TH) significantly reduces mortality and morbidities in neonates with Neonatal Encephalopathy (NE). NE may result in neonatal death and multisystem organ impairment, including acute kidney injury (AKI). Our study aimed to utilize machine learning (ML) methods to predict the outcome of TH-treated NE neonates developing AKI and death during TH. In this retrospective multinational study, 1149 TH-treated NE neonates and 801 controls were included. AKI was classified using KDIGO neonatal criteria based on serum creatinine measurements. The ML model incorporated gestational age, birth weight, postnatal age, and serum creatinine values. The algorithm used all these covariates to predict one of five outcomes: survival with/without AKI, mortality with/without AKI, and hospitalized non-NE controls. The XGBoost model achieved an AUC of 95% and an accuracy of 75.08% in predicting AKI and survival, surpassing other ML classifiers that demonstrated accuracy levels ranging from 54% to 65%. To our knowledge this is the first ML model trained on multicenter, multinational data specifically aimed at predicting neonates' AKI, death, and survival within the first three days. Our ML scoring systems' code and user interface are freely available ( https://github.com/NUBagciLab/Therapeutic-Hypothermia-Outcome-Classification , https://thprediction.streamlit.app/ ). This tool has potential to support neonatologists to personalize therapies, and to optimize pharmacotherapy for renally cleared drugs.