AbstractCurrently, microbial manufacturing is widely used in various fields, such as food, medicine and energy, for its advantages of greenness and sustainable development. Process optimization is the committed step enabling the commercialization of microbial manufacturing products. However, the present optimization processes mainly rely on experience or trial-and-error method ignoring the intrinsic connection between cellular physiological requirement and production performance, so in many cases the productivity of microbial manufacturing could not been fully exploited at economically feasible cost. Recently, the rapid development of omics technologies facilitates the comprehensive analysis of microbial metabolism and fermentation performance from multi-levels of molecules, cells and microenvironment. The use of omics technologies makes the process optimization more explicit, boosting microbial manufacturing performance and bringing significant economic benefits and social value. In this paper, the traditional and omics technologies-guided process optimization of microbial manufacturing are systematically reviewed, and the future trend of process optimization is prospected.