Our article analyzes the main biological potentials and economic barriers of using Miscanthus as a new energy crop in agricultural practice in the Czech Republic and the Central-Eastern European region. We have used primary data from long-term field experiments and commercial plantations to create production and economic models that also include an analysis of competitive ability with conventional crops. Our results showed that current economic conditions favor annual crops over Miscanthus (for energy biomass) and that this new crop shows very good adaptation to the effects of climate change. Selected clones of Miscanthus × giganteus reached high biomass yields between 15–17 t DM ha⁻¹ y⁻¹ despite very dry and warm periods and low-input agrotechnology, and they have good potential to become important biomass crops for future bioenergy and the bioeconomy. Key barriers and factors are identified, including gene pool and agronomy improvement, change of subsidy policy (Common agriculture policy-CAP), climate change trends, and further development of the bioeconomy.