Objectives: The objectives of this study are to construct the high definition phenotype (HDP), a novel time-series data structure composed of both primary and derived parameters, using heterogeneous clinical sources and to determine whether different predictive models can utilize the HDP in the neonatal intensive care unit (NICU) to improve neonatal mortality prediction in clinical settings. Materials and Methods: A total of 49 primary data parameters were collected from July 2018 to May 2020 from eight level-III NICUs. From a total of 1546 patients, 757 patients were found to contain sufficient fixed, intermittent, and continuous data to create HDPs. Two different predictive models utilizing the HDP, one a logistic regression model (LRM) and the other a deep learning long–short-term memory (LSTM) model, were constructed to predict neonatal mortality at multiple time points during the patient hospitalization. The results were compared with previous illness severity scores, including SNAPPE, SNAPPE-II, CRIB, and CRIB-II. Results: A HDP matrix, including 12 221 536 minutes of patient stay in NICU, was constructed. The LRM model and the LSTM model performed better than existing neonatal illness severity scores in predicting mortality using the area under the receiver operating characteristic curve (AUC) metric. An ablation study showed that utilizing continuous parameters alone results in an AUC score of >80% for both LRM and LSTM, but combining fixed, intermittent, and continuous parameters in the HDP results in scores >85%. The probability of mortality predictive score has recall and precision of 0.88 and 0.77 for the LRM and 0.97 and 0.85 for the LSTM. Conclusions and Relevance: The HDP data structure supports multiple analytic techniques, including the statistical LRM approach and the machine learning LSTM approach used in this study. LRM and LSTM predictive models of neonatal mortality utilizing the HDP performed better than existing neonatal illness severity scores.