Engineering microorganisms capable of accumulating multiple products are sometimes attractive because they yield several advantages in balancing the in vivo metabolic flux and restoring the optimal cell physiology. With the development of metabolic engineering and synthetic biology, numerous strategies for minimizing the substrate waste, optimizing the product portfolios, and maximizing the product yield in co-production systems have been designed and applied. This paper reviewed the recent developments in this field and discussed the challenges that may be encountered during the scaling up of the co-production systems. Finally, the importance of product portfolios and biorefinery strategy of single-cell in co-production processes was proposed.