Synthesis gas (syngas) fermentation represents a promising biological method for converting industrial waste gases, particularly carbon monoxide (CO) and carbon dioxide (CO2) from industrial sources (e.g. steel production or municipal waste gasification), into high-value products such as biofuels, chemicals, and animal feed using acetogenic bacteria. This review identifies and addresses key challenges that hinder the large-scale adoption of this technology, including limitations in gas mass transfer, an incomplete understanding of microbial metabolic pathways, and suboptimal bioprocess conditions. Our findings emphasize the critical role of microbial strain selection and bioprocess optimization to enhance productivity and scalability, with a focus on utilizing diverse microbial consortia and efficient reactor systems. By examining recent advancements in microbial conditioning, operational parameters, and reactor design, this study provides actionable insights to improve syngas fermentation efficiency, suggesting pathways towards overcoming current technical barriers for its broader industrial application beyond the production of bulk chemicals.