This study evaluates the performance of alternative powertrains for Class 8 heavy-duty trucks under various 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 2024, 2035, and 2050, considering anticipated technological advancements. The analysis employed simulation models that accurately reflect vehicle dynamics, powertrain components, and energy storage systems, leveraging real-world driving data. An integrated simulation workflow was implemented using Argonne National Laboratory's POLARIS, SVTrip, Autonomie, and TechScape software. Additionally, a sensitivity analysis was performed to assess how fluctuations in energy and fuel costs impact the cost-effectiveness of various powertrain options. By 2035, battery electric trucks (BEVs) demonstrate strong cost competitiveness in the 0-250 mile and 250-500 mile ranges, especially when primarily charged at depots. Fuel cell electric vehicles (FCEVs) remain competitive in the 250-500-mile range, particularly under higher diesel prices. For distances over 500 miles, FCEVs become the preferred solution, providing greater range and operational flexibility. By 2050, technological advancements and reduced truck costs further enhance the feasibility of both BEVs and FCEVs. The BEV500 shows improved efficiency and resilience to energy price fluctuations, making it viable for medium-range operations and cost-effective even with high en-route electricity rates. FCEVs are expected to remain competitive in both medium and long-range operations, especially when diesel prices are elevated, positioning them as strong alternatives to conventional powertrains for long-haul routes.