Developing and prescribing drugs for arrhythmias is a complex challenge. Typically, a trial-and-error approach is used to identify effective antiarrhythmic medications for each patient, a process that can take years and expose individuals to serious side effects. This is partly due to the fact that arrhythmia is a multifaceted condition that remains poorly understood. The variability in ion channels and transporters that shape cardiomyocyte action potentials and facilitate the heart's rhythmic contractions adds to the complexity of the disease. Cell-to-cell heterogeneity can render some cardiomyocytes more resilient to arrhythmogenic challenges; however, the differences in ion-channel conductance profiles between arrhythmia-resistant and arrhythmia-susceptible cells are not yet well understood. In this thesis, we present an algorithm designed to investigate the combinations of ion-channel conductances that increase arrhythmia resistance in a whole-cell ventricular cardiomyocyte model. We use repolarization reserve current (RRC) as a metric for arrhythmia resistance, where lower magnitudes are associated with a higher risk of proarrhythmia. This work improves our understanding of how differences in ion-channel conductance profiles influence RRC values and arrhythmia susceptibility, which is crucial given the variability in risk among patients. We also applied our pipeline to an induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model. iPSC-CMs are widely used for studying cardiac arrhythmia mechanisms and offer a patient-specific system that reflects an individual’s genetic makeup at both cellular and ion-channel levels. However, they do not perfectly mimic adult heart cells. Using our pipeline on both adult and iPSC-derived in silico cardiomyocyte models, we can compare and identify differences in their repolarization and response to proarrhythmic substrates. Our optimization of the adult cardiomyocyte model improved RRC by up to 84% and enhanced resistance to arrhythmogenic insults. The optimized conductance profiles revealed new insights, including the previously unreported role of the late sodium current. This computational approach provides a systems-level quantification of repolarization reserve and highlights key mechanistic differences between adult and iPSC-derived cardiomyocytes. A better understanding of repolarization reserve is important as it could improve arrhythmia mitigation strategies, resulting in better outcomes for individual patients.