Industrial and military vehicles, including trucks, tanks and others, employ cooling systems that address passenger cooling and auxiliary cooling loads ranging from a few Watts to 50 kW or more. Such systems are typically powered using vapor-compression cooling systems that either directly supply cold air to the various locations, or cool an intermediate single-phase coolant closed loop, which in turn serves as the coolant for the passenger cabins and auxiliary loads such as electronics modules. Efforts are underway to enhance the performance of such systems, and also to develop more light weight and compact systems that would remove high heat fluxes. The distributed cooling configuration offers the advantage of a smaller refrigerant system package. The heat transfer between the intermediate fluid and air or with the auxiliary heat loads can be fine tuned through the control of flow rates and component sizes and controls to maintain tight tolerances on the cooling performance. Because of the additional loop involved in such a configuration, there is a temperature penalty between the refrigerant and the ultimate heat sink or source, but in some configurations, this may be counteracted through judicious design of the phase change-to-liquid coupled heat exchangers. Such heat exchangers are inherently smaller due to the high heat transfer coefficients in phase change and single-phase liquid flow compared to air flow. The additional loop also requires a pump to circulate the fluid, which adds pumping power requirements. However, a direct refrigerant-to-heat load coupling system might in fact be suboptimal if the heat loads are distributed across large distances. This is because of the significantly higher pressure drops (and saturation temperature drops) incurred in transporting vapor or two-phase fluids through refrigerant lines across long plumbing elements. An optimal system can be developed for any candidate application by assessing the tradeoffs in cooling capacity, heat exchanger sizes and configurations, and compression, pumping and fan power. In this study, a versatile simulation platform for a wide variety of direct and indirectly coupled cooling systems was developed to enable comparison of different component geometries and system configurations based on operating requirements and applicable design constraints. Components are modeled at increasing levels of complexity ranging from specified closest approach temperatures for key components to models based on detailed heat transfer and pressure drop models. These components of varying complexity can be incorporated into the system model as desired and trade-off analyses on system configurations performed. Employing this platform as a screening, comparison, and optimization tool, a number of conventional vapor-compression and distributed cooling systems were analyzed to determine the efficacy of the distributed cooling scheme in mobile cooling applications. Four systems serving approximately a 6 kW cooling duty, two with air-coupled evaporators and two with liquid-coupled evaporators, were analyzed for ambient conditions of 37.78°C and 40% relative humidity. Though the condensers and evaporators are smaller in liquid-coupled systems, the total mass of the heat exchangers in the liquid-coupled systems is larger due to the additional air-to-liquid heat exchangers that the configuration requires. Additionally, for the cooling applications considered, the additional compressor power necessitated by the liquid-coupled configuration and the additional power consumed by the liquid-loop pumps result in the coefficient of performance being lower for liquid-coupled systems than for air-coupled systems. However, the use of liquid-coupling in a system does meet the primary goal of decreasing the system refrigerant inventory by enabling the use of smaller condensers and evaporators and by eliminating long refrigerant carrying hoses.