The heavy-duty road transport sector is critical to European trade and socio-economic development, moving millions of tons of goods within and to neighboring countries, and this depends on fleets of diesel trucks. The path to decarbonization in Europe will require joint efforts from multiple stakeholders and significant investments in technological development, infrastructure and fuel production. This study assesses the available drivetrains to meet the European Union’s carbon reduction targets, and provides insight into the future market segmentation from the perspective of the transport companies. It quantifies selection criteria by setting a mixed-integer linear programming problem to optimize the total cost of ownership of transport, while complying with carbon reduction targets set by the European Union, and discusses underlying factors that may play a significant role. The results show that there will be significant segmentation and diversification in drivetrain technology in the short to medium term, including zero-emission, low-emission and conventional fossil technologies, as economics and carbon reduction targets play a major role in determining the composition of future truck fleets. Ultimately, fossil-based vehicles could be entirely phased out in favor of zero-emission trucks, where the market share is split between battery electric and fuel cell electric vehicles. Key factors influencing this segmentation are the price of fuel, availability of bio-based fuels and the role of emission regulation, in particular the scope and severity of future carbon reduction targets. Furthermore, underlying implications may also have important consequences, including customer perspective towards new technologies, renewable energy intermittency, security of supply, critical material supply chains, and the significant infrastructure upgrade and development costs. The degree to which these issues will affect the future transport market is unknown.