As metabolic engineering moves beyond static pathway optimization toward programmable cell factory design, dynamic metabolic control, and spatiotemporal regulation have emerged as key strategies for enhancing the efficiency, robustness, and adaptability of microbial biomanufacturing. Conventional static engineering approaches, including promoter replacement, gene overexpression, and pathway deletion, have enabled the biosynthesis of diverse chemicals and natural products. However, fixed genetic configurations are often unable to accommodate the dynamic physiological states that arise during cultivation, particularly under metabolic burden, intermediate toxicity, and growth–production trade-offs. Dynamic metabolic control addresses these limitations by sensing intracellular and extracellular cues to enable adaptive flux redistribution and decouple growth from production. Spatiotemporal regulation further extends this framework by coordinating both the timing and localization of pathway activities through enzyme co-localization, scaffold-guided assembly, compartmentalization, and division of labor in microbial consortia. Together, these strategies provide a conceptual and engineering framework for the rational design of next-generation microbial cell factories and for advancing more efficient and programmable biomanufacturing systems.