Microbial cell factories have emerged as sustainable platforms for producing bio-commodities such as biofuels, bioplastics, and pharmaceuticals. However, achieving industrial scalability remains hindered by challenges in strain robustness, including genetic instability, metabolic burden, and environmental stress tolerance. This review explores cutting-edge strategies in microbial engineering to enhance robustness, focusing on synthetic biology tools, adaptive laboratory evolution (ALE), and systems biology approaches. We discuss advances in genome-scale modeling, microbial consortia design, and resilience engineering to optimize performance in large-scale bioreactors. Case studies highlight successful applications of E. coli, S. cerevisiae, and cyanobacteria for producing compounds like polyhydroxyalkanoates (PHAs) and isoprenoids. By integrating computational predictions with experimental validation, this review underscores the importance of robustness as a cornerstone for economically viable biomanufacturing. Finally, we propose a roadmap for bridging lab-scale innovations to industrial deployment, emphasizing the synergy between metabolic flexibility and process engineering.
