There is a renewed interest in acetone-butanol-ethanol (ABE) fermentation from renewable substrates for the sustainable and environment-friendly production of biofuel and platform chemicals. However, the ABE fermentation is associated with several challenges due to the presence of heterogeneous components in the renewable substrates and the intrinsic characteristics of ABE fermentation process. Hence, there is a need to select optimal substrates and modify their characteristics suitable for the ABE fermentation process or microbial strain. This "designed biomass" can be used to establish the consolidated bioprocessing systems. As there are very few reports on designed biomass, the main objectives of this review are to summarize the main challenges associated with ABE fermentation from renewable substrates and to introduce feasible strategies for designing the substrates through pretreatment and hydrolysis technologies as well as through the establishment of consolidated bioprocessing systems. This review offers new insights on improving the efficiency of ABE fermentation from designed renewable substrates.