In order to reduce greenhouse gas (GHG) emissions, fleets of medium- and heavy-duty vehicles are transitioning from conventional fossil fuels to fully electric drivetrains. To utilize these medium- and heavy-duty electric vehicles (MHDEVs) without significantly disrupting their operations, Megawatt Charging Systems (MCS) are being developed, which enable charging rates up to 4.5 MW. However, these charging rates are associated with substantial heat generation in the vehicle’s battery pack. To regulate the battery temperature and maximize battery lifetime, performance, and safety, the development of a battery thermal management system (BTMS) for this application is crucial. The study provides a methodology that adopted a system engineering approach for the design of a BTMS for the application of MHDEVs which utilize MCS. The study defined the requirements for the BTMS which include the optimal temperature range for battery cells and determined the battery heat generation rate when using MCS. Furthermore, the study investigated the magnitude of temperature gradients in battery cells as a result of MCS. Subsequently, two assessment stages have been proposed to assess BTMS strategies, which include forced air BTMS, immersion cooling BTMS, cooling plates with coolant BTMS, and cooling plates with refrigerant BTMS. This assessment resulted in design requirements for heat transfer areas and mass flow rates to maintain the battery cells below 35 ℃. Moreover, the concepts of utilizing cooling plates with refrigerant in a vapor-compression refrigeration system and storing charging session heat by thermal energy storage (TES) have been developed. This included the dimensioning of a condenser and compressor for the vapor-compression refrigeration cycle and included the dimensioning of the required mass and volume of TES medium for the TES system. The study found that these two BTMS strategies are the most favorable. Thermal energy storage with hydrated salt as phase change material (PCM) appeared as the most effective and feasible option subsequent to conducting comparisons with immersion coolant and paraffin PCM. However, a BTMS with a vapor compression refrigeration system might be needed when the BTMS is used for both driving and charging. Analysis of refrigerants R717, R134a, and R1234yf, indicated that R717 is the most effective in this BTMS with a COP of 3.52 and a lower required mass flow rate and compressor power consumption, however, is associated with several safety considerations that must be addressed when selecting R717 over other refrigerants. Lastly, the study utilized a MATLAB Simulink model to identify the effects of dynamic phenomena that occur during operation of the BTMS and the study determined the impact of BTMS weight on MHDEV driving range. Recommendations for future research are given related to the need for increased fidelity of heat generation prediction and BTMS models. Furthermore, future research should be conducted on combining the BTMS with other thermal management systems in the vehicle to maximize overall effectiveness.