Lithium-Ion batteries used for electric vehicle applications are subject to large currents and various operation conditions, making battery pack design and life extension a challenging problem. With increase in complexity, modeling and simulation can lead to insights that ensure optimal performance and life extension. In this manuscript, an electrochemical-thermal (ECT) coupled model for a 6 series × 5 parallel pack is developed for Li ion cells with NCA/C electrodes and validated against experimental data. Contribution of the cathode to overall degradation at various operating conditions is assessed. Pack asymmetry is analyzed from a design and an operational perspective. Design based asymmetry leads to a new approach of obtaining the individual cell responses of the pack from an average ECT output. Operational asymmetry is demonstrated in terms of effects of thermal gradients on cycle life, and an efficient model predictive control technique is developed. Concept of reconfigurable battery pack is studied using detailed simulations that can be used for effective monitoring and extension of battery pack life.