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Medium trucks constitute a large market segment of the commercial transportation sector, and are also used widely for military tactical operations. Recent technological advances in hybrid powertrains and fuel cell auxiliary power units have enabled design alternatives that can improve fuel economy and reduce emissions dramatically. However, deterministic design optimization of these configurations may yield designs that are optimal with respect to performance but raise concerns regarding the reliability of achieving that performance over lifetime. In this article we identify and quantify uncertainties due to modeling approximations or incomplete information. We then model their propagation using Monte Carlo simulation and perform sensitivity analysis to isolate statistically significant uncertainties. Finally, we formulate and solve a series of reliability-based optimization problems and quantify tradeoffs between optimality and reliability.