The truck sector produces one-fourth of the greenhouse gas emissions in Italy. Therefore, it calls for an urgent emission reduction to achieve the national mid-century net-zero pledges. In this work, a methodology is developed, based on a model for estimating the long-term energy transitions, the ModUlar energy system Simulation Environment (MUSE), to project the long-term freight heavy-duty sector evolution in Italy. The methodology applies a bottom-up description of the sector, where technologies are characterised in terms of costs, efficiencies, and emissions. Results show that efficiency improvements and technological cost reduction due to learning can only reduce the sector emissions by a limited amount. In fact, although, lowering costs of alternative powertrains and fuels will have a significant effect on reducing tailpipe emissions, this should occur alongside a ban of internal combustion engines. Additional renewable generation should need to grow between 30 and 64 TW/y to substantially reduce emissions and leading to a zero-tailpipe truck sector by 2050. The replacement of conventional engines by alternative powertrains remains dependent on distribution and fuelling infrastructure expansion, which should go hand in hand with the promotion of electric and hydrogen-fuelled vehicles.