Energy consumption and the associated environmental impact are a pressing challenge faced by the transportation sector. Emerging electric-drive vehicles have shown promises for substantial reductions in petroleum use and vehicle emissions. Their success, however, has been hindered by the limitations of energy storage technologies. Existing in-vehicle Lithium-ion battery systems are bulky, expensive, and unreliable. Energy storage system (ESS) design and optimization is essential for emerging transportation electrification. This paper presents an integrated ESS modeling, design and optimization framework targeting emerging electric-drive vehicles. Based on an ESS modeling solution that considers major run-time and long-term battery effects, the proposed framework unifies design-time optimization and run-time control. It conducts statistical optimization for ESS cost and lifetime, which jointly considers the variances of ESS due to manufacture tolerance and heterogeneous driver-specific...