This study introduces a simulation-based analysis of the decarbonization options for the road freight transport sector. It focuses on exploring the impact of operational and management measures on fleet renewal strategies aimed at achieving net zero goals by 2050. The proposed approach integrates current and planned future policy changes, operational practices, and technology renewal into the modeling process to offer a macro-level perspective on the decarbonization challenge. Specifically, the proposed modeling approach takes into account the reduction of empty trips, the optimization of cargo consolidation, and the promotion of eco-driving practices based on national freight transport data (i.e., covering more than 7.99 million trips). The proposed approach examines the effect of introducing contemporary vehicle technologies, such as new diesel vehicles (EURO VI or higher), new natural gas vehicles (EURO VI or higher), electric vehicles and hydrogen vehicles, as feasible replacements for aging vehicles powered by conventional fossil fuels. The adoption of these cleaner and newer technologies demonstrates the potential for emissions reductions of up to 13% (2,070,000 tons CO2e) by 2030 and 47% (13,232,000 tons CO2e) by 2050. In addition, the results obtained from this research can serve as an exemplary case study for other emerging economies.