Fossil fuel use drives greenhouse gas emissions and climate change, highlighting the need for alternatives like biomass-derived syngas. Syngas, mainly H2 and CO, is produced via biomass gasification and offers a solution to environmental challenges. Syngas fermentation through the Wood-Ljungdahl pathway yields valuable chemicals under mild conditions. However, challenges in scaling up persist due to issues like unpredictable syngas composition and microbial fermentation contamination. This review covers advancements in genetic tools and metabolic engineering to expand product range, highlighting crucial enabling technologies that expedite strain development for acetogens and other non-model organisms. This review paper provides an in-depth exploration of syngas fermentation, covering microorganisms, gas composition effects, separation techniques, techno economic analysis, and commercialization efforts.