The greenhouse gas CO₂ is of considerable and particular interest for use as a next generation feedstock in different types of bioconversions to create valuable products on a large scale. However, this gaseous subsrate is a highly stable molecule with strong C=O bonds, non-polarity, low electron, and proton affinity, posing challenges for efficient enzymatic bioconversion in aqueous media. To demonstrate the construction of efficient catalytic systems, in this review, we first discuss recent advances in engineering enzyme structures and optimal microenvironments to improve the bioactivation efficiency of CO₂ to C₁ compounds. Based on these understandings, we then discuss the construction of artificial multi-enzymatic cascade reaction pathways or enzyme-assisted microbial synthesis pathways for further conversion to multicarbon compounds from CO₂. Finally, we highlight the perspectives of microenvironment controlling enzymatic bioconversion of CO₂ as feedstock for a future sustainable world.