Nasopharyngeal cancer (NPC) has a unique histopathology compared with other head and neck cancers. Individual NPC patients may attain different outcomes. This study aims to build a prognostic system by combining a highly accurate machine learning model (ML) model with explainable artificial intelligence to stratify NPC patients into low and high chance of survival groups. Explainability is provided using Local Interpretable Model Agnostic Explanations (LIME) and SHapley Additive exPlanations (SHAP) techniques. A total of 1094 NPC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database for model training and internal validation. We combined five different ML algorithms to form a uniquely stacked algorithm. The predictive performance of the stacked algorithm was compared with a state-of-the-art algorithm—extreme gradient boosting (XGBoost) to stratify the NPC patients into chance of survival groups. We validated our model with temporal validation (n = 547) and geographic external validation (Helsinki University Hospital NPC cohort, n = 60). The developed stacked predictive ML model showed an accuracy of 85.9% while the XGBoost had 84.5% after the training and testing phases. This demonstrated that both XGBoost and the stacked model showed comparable performance. External geographic validation of XGBoost model showed a c-index of 0.74, accuracy of 76.7%, and area under curve of 0.76. The SHAP technique revealed that age of the patient at diagnosis, T-stage, ethnicity, M-stage, marital status, and grade were among the prominent input variables in decreasing order of significance for the overall survival of NPC patients. LIME showed the degree of reliability of the prediction made by the model. In addition, both techniques showed how each feature contributed to the prediction made by the model. LIME and SHAP techniques provided personalized protective and risk factors for each NPC patient and unraveled some novel non-linear relationships between input features and survival chance. The examined ML approach showed the ability to predict the chance of overall survival of NPC patients. This is important for effective treatment planning care and informed clinical decisions. To enhance outcome results, including survival in NPC, ML may aid in planning individualized therapy for this patient population.