This paper presents an optimization modeling approach to support strategic planning for designing hydrogen supply chain (HSC) networks. The energy source for hydrogen production is proposed to be electricity generated at Mexican sugar factories. This study considers the utilization of existing infrastructure in strategic areas of the country, which brings several advantages in terms of possible solutions. This study aims to evaluate the economic and environmental implications of using biomass wastes for energy generation, and its integration to the national energy grid, where the problem is addressed as a mixed-integer linear program (MILP), adopting maximization of annual profit, and minimization of greenhouse gas emissions as optimization criteria. Input data is provided by sugar companies and the national transport and energy information platform, and were represented by probability distributions to consider variability in key parameters. Independent solutions show similarities in terms of resource utilization, while also significant differences regarding economic and environmental indicators. Multi-objective optimization was performed by a genetic algorithm (GA). The optimal HSC network configuration is selected using a multi-criteria decision technique, i.e., TOPSIS. An uncertainty analysis is performed, and main economic indicators are estimated by investment assessment. Main results show the trade-off interactions between the HSC elements and optimization criteria. The average internal rate of return (IRR) is estimated to be 21.5% and average payback period is 5.02 years.