Purpose <p>The transition from fossil fuels to alternative fuels (AFs) is essential for reducing the environmental impact of the heavy-duty vehicle (HDV) sector. Identifying the most sustainable AFs requires a comprehensive understanding of their performance across environmental, economic, and social dimensions, typically evaluated through life cycle assessment (LCA) and life cycle sustainability assessment (LCSA). This study aims to identify research gaps in the literature and to evaluate the sustainability performance of alternative-fuel heavy-duty vehicles (HDVs). The research specifically investigates how existing studies cover fuel types and vehicle technologies, the methodological approaches and life cycle boundaries they adopt, and the extent to which sustainability indicators are integrated and reported. Additionally, the meta-analysis aims to provide a basis for comparing some environmental impact categories across different studies in the literature.</p> Methods <p>A comprehensive systematic literature review of 44 peer-reviewed articles is conducted. The review analyzes the coverage of fuel types and vehicle technologies, the methodological choices such as hybrid life cycle assessment (LCA) approaches and system boundaries, and the integration and transparency of sustainability indicators in life cycle sustainability assessment (LCSA). Furthermore, a comprehensive meta-analysis is conducted to provide a benchmarking of the results from the literature.</p> Results <p>The review reveals that hydrogen and electric HDVs, while offering significant environmental potential, continue to face challenges related to high life-cycle costs and dependence on upstream energy sources. Research disproportionately emphasizes buses (68%) over trucks (32%), with electric and diesel fuels being the most frequently analyzed. Methodologically, hybrid LCAs dominate (56%), and well-to-wheel assessments account for most analyses (84%), often overlooking upstream processes (e.g., raw material extraction) and downstream phases (e.g., end-of-life). Full LCAs demonstrate that hydrogen and electric HDVs powered by renewable energy achieve the lowest greenhouse gas (GHG) emissions, while their fossil-based counterparts perform among the worst in fuel-specific assessments. On the economic front, life-cycle cost is the most widely assessed indicator, with diesel, compressed natural gas (CNG), and liquefied natural gas (LNG) consistently showing cost advantages. In contrast, social sustainability remains the least explored dimension.</p> Conclusions <p>The findings emphasize the urgent need for methodological standardization, stronger attention to social sustainability, and explicit consideration of regional contexts. Addressing these gaps is essential to generating balanced, policy-relevant assessments of AFs in the HDVs sector.</p>