Decarbonizing the transportation sector is one of the key challenges to reduce greenhouse gas (GHG) emissions and meet EU Green deal 2030 targets. Road transport decarbonization requires a holistic approach encompassing various strategies and interventions aimed at fostering the sustainable transition of this sector. This challenge is crucial given that road is responsible for over 90% of the overall transport GHG emissions.Within this framework, this study aims, for the Italian case, to: a) estimate the national passenger and freight road travel demand with respect to three different time periods: 2005 (reference year for EU “fit for 55” target); 2019 (last consolidated pre-covid year); 2022 (base-line year); b) define possible road transport scenarios to 2030 following the Avoid-Shift-Improve (ASI) approach; c) estimate the GHG and energy consumption inventory related to national road transport for the 2005, 2019; 2022 and 2030 scenarios. Due to the current “deep uncertainty” regarding key economic and social variables in this period, two forecasting scenarios – named “moderate decarbo” and “high decarbo” – were designed and based on different and somewhat opposite hypotheses on exogenous variables (e.g., GDP) and penetration rates of measures and policies promoting sustainable transportation (e.g., subsidies for electric vehicles) already in place. Although the current European legislation refers only to Tank-to-Wheel (TtW) objectives, this study included also the Well-to-Wheel (WtW) evaluation, which is more accurate in assessing the GHG impact of different policies, energy carriers, and technologies. As for the past, results suggest that GHG reductions over the period 2005–2022 are mostly due to crises and stagnation of the Italian economy. “Moderate decarbo” forecasts for 2030 lead to a 12% reduction of TtW (and 15% for WtW) GHG emissions compared to 2005 levels, with ASI policies compensating for the assumed economic growth. In any case these values are far from the EU “Fit for 55” goal setting a 43.7% reduction of TtW emissions. Even under very favourable hypotheses (“high decarbo” scenario), GHG emissions might be reduced by only 28% for TtW and 33% for WtW, still well below EU objectives. Furthermore, passengers and freight show very different behaviour, with the latter contributing to emissions more than proportionally, and “shift-to-rail” policies, although very useful in some market segments, contribute moderately at the overall national level. The main conclusion of this study is that the pathway towards road transport decarbonization in Italy (and possibly in other EU Countries) is very uncertain, and the ambitious 2030 target is unlikely to be met with currently planned policies alone. The transportation system needs to be constantly monitored, and new policies have to be implemented to reach higher emissions reduction goals.