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This work aims at addressing the challenge of reconciling the surge in road transportation with the need to reduce CO2 emissions. The research particularly focuses on exploring the potential of fuel cell technology in long-distance road haulage, which is currently a major solution proposed by relevant manufacturers to get zero local emissions and an increased total payload. Specifically, a methodology is applied to enable rapid and accurate identification of techno-economically effective fuel cell hybrid heavy-duty vehicle (FCH2DV) configurations. This is possible by performing model-based co-design of FCH2DV powertrain and related control strategies. Through the algorithm, it is possible to perform parametric scenario analysis to better understand the prospects of this technology in the decarbonization path of the heavy-duty transportation sector, changing in an easy way all the parameters involved.