The overutilization of the healthcare system has been a significant issue financially and politically, placing burdens on the government, patients, providers and individual payers. In this dissertation, we study how mathematical models and computational models can be utilized to support healthcare decision-making and generate effective interventions for healthcare overcrowding. We focus on applying operations research and data mining methods to mitigate the overutilization of emergency department and inpatient services in four scenarios. Firstly, we systematically review research articles that apply analytical queueing models to the study of the emergency department, with an additional focus on comparing simulation models with queueing models when applied to similar research questions. Secondly, we present an agent-based simulation model of epidemic and bioterrorism transmission, and develop a prediction scheme to differentiate the simulated transmission patterns during the initial stage of the event. Thirdly, we develop a machine learning framework for effectively selecting enrollees for case management based on Medicaid claims data, and demonstrate the importance of enrolling current infrequent users whose utilization of emergency visits might increase significantly in the future. Lastly, we study the role of temporal features in predicting future health outcomes for diabetes patients, and identify the levels to which the aggregation can be most informative.