Electromobility has gained significance over recent years and the requirements on the performance and efficiency of electric vehicles are growing. Lithium-ion batteries are the primary source of energy in electric vehicles and their performance is highly dependent on the operating temperature. There is a compelling need to create a robust modeling framework to drive the design of vehicle batteries in the ever-competitive market. This paper presents a system-level modeling methodology for thermal simulations of large battery packs for electric trucks under real-world operating conditions. The battery pack was developed in GT-SUITE, where module-to-module discretization was performed to study the thermal behavior and temperature distribution within the pack. The heat generated from each module was estimated using Bernardi’s expression and the pack model was calibrated for thermal interface material properties under a heat-up test. The model evaluation was performed for four charging/discharging and cooling scenarios typical for truck operations. The results show that the model accurately predicts the average pack temperature, the outlet coolant temperature and the state of charge of the battery pack. The methodology developed can be integrated with the powertrain and passenger cabin cooling systems to study complete vehicle thermal management and/or analyze different battery design choices.