Most current biotechnology industries are based on batch or fed-batch fermentation processes, which often show low productivity and high production costs compared to chemical processes. To increase the economic competitiveness of biological processes, continuous fermentation technologies are being developed that offer significant advantages in comparison with batch/fed-batch fermentation processes, including: (1) removal of potential substrates and product inhibition, (2) prolonging the microbial exponential growth phase and enhancing productivity, and (3) avoiding repeated fermentation preparation and lowering operation and installation costs. However, several key challenges should be addressed for the industrial application of continuous fermentation processes, including (1) contamination of the fermentation system, (2) degeneration of strains, and (3) relatively low product titer. In this study, we reviewed and discussed metabolic engineering and synthetic biology strategies to address these issues.