This thesis work presents detailed results of the application of exergy-based methods to highly dynamic, integrated aerospace systems such as hypersonic vehicle concepts. In particular, an exergy-based methodology is compared to a more traditional based measure by applying both to the synthesis/design and operational optimization of a hypersonic vehicle configuration comprised of an airframe sub-system and a propulsion sub-system consisting of inlet, combustor, and nozzle components. A number of key design and operational decision variables are identified as those which govern the hypersonic vehicle flow physics and thermodynamics and detailed one-dimensional models of each component and sub-system are developed. Rates of exergy loss as well as exergy destruction resulting from irreversible loss mechanisms are determined in each of the hypersonic vehicle sub-systems and their respective components. Multiple optimizations are performed for both the propulsion sub-system only and for the entire hypersonic vehicle system for single mission segments and for a partial, three-segment mission. Three different objective functions are utilized in these optimizations with the specific goal of comparing exergy methods to a standard vehicle performance measure, namely, the vehicle overall efficiency. Results of these optimizations show that the exergy method presented here performs well when compared to the standard performance measure and, in a number of cases, leads to more optimal syntheses/designs in terms of the fuel mass flow rate required for a given task (e.g., for a fixed-thrust requirement or a given mission). In addition to the various vehicle design optimizations, operational optimizations are conducted to examine the advantage if any of energy exchange to maintain shock-on-lip for both design and off-design conditions. Parametric studies of the hypersonic vehicle sub-systems and components are also conducted and provide further insights into the impacts that the design and operational decision variables and flow properties have on the rates of exergy destruction. / Master of Science