Results from past research and research recently initiated are presented here in order to illustrate the need for a multi-fidelity (higher- and reduced-order) dynamic modeling, simulation, and optimization capability that results in aircraft subsystem integrations that minimize waste heat generation and reduce overall system energy requirements across a range of mission profiles. The examples presented provide a basis for the work envisioned as well as illustrations of the non-equilibrium thermodynamic effects of unsteady or transient operation on aircraft synthesis/design and operation. The three examples given involve i) the mission-integrated synthesis/design optimization of an advanced tactical aircraft system with a focus on its transient fuel loop subsystem, ii) the effects of mission segment discretizations on capturing the dynamics of a scram-jet hypersonic vehicle mission on vehicle performance, and iii) the effects of unsteady aerodynamics on flight vehicle operation.