Rising energy demands and the environmental impact of fossil fuel combustion have promoted a growing interest in alternative fuel sources. Biobutanol is a promising biofuel that can be used as a partial or complete substitute for petrol in unmodified internal combustion engines. It can be produced through a microbiological process called ABE fermentation. Currently, its production is uncompetitive in the market, but researchers are still working on solutions to improve the technology. This paper used a multi-criteria decision analysis method to evaluate different alternatives for biobutanol production: microorganism strain, agro-industrial waste substrate as process feedstock, bioreactor type and extraction method. It was determined that C. beijerinckii and C. saccharoperbutylacetonicum have great potential for being used for efficient biobutanol production. Cheese whey is a promising residue for being used in the fermentation medium. Other residues evaluated in the paper gained similar results as being “close to ideal”. Fed-batch with immobilized cells was chosen as the most promising fermentation method. It showed the greatest prospects as an optimal way to produce butanol. And, finally, adsorption and liquid-liquid extraction methods were identified as the most promising for ABE product extraction in comparison to others. Identified combinations of optimal solutions for microorganisms, fermentation methods, substrates and extraction techniques should be further evaluated in the laboratory setting.