This study evaluates the performance of alternative powertrains for Class 8 heavy-duty trucks under a variety of real-world driving conditions, cargo loads, and operating ranges. Energy consumption, greenhouse gas emissions, and the Levelized Cost of Driving (LCOD) were assessed for different powertrain technologies in 2023, 2035, and 2050, considering anticipated technological advancements. The analysis was conducted using simulation models that accurately reflect vehicle dynamics, powertrain components, and energy storage systems, leveraging real-world driving data. The Argonne National Laboratory's POLARIS, SVTrip, Autonomie, and TechScape software were used in an integrated simulation workflow for this analysis. Additionally, a sensitivity analysis was conducted on fuel and battery costs to understand their impact on economic outcomes. The study considered a hydrogen cost of $4/kg in 2035 and 2050, three AEO2023 low, medium, high diesel cost scenarios, and electricity costs ranging