Xanthophyll is an oxidated version of carotenoid. It presents significant value to the pharmaceutical, food, and cosmetic industries due to its specific antioxidant activity and variety of colors. Chemical processing and conventional extraction from natural organisms are still the main sources of xanthophyll. However, the current industrial production model can no longer meet the demand for human health care, reducing petrochemical energy consumption and green sustainable development. With the swift development of genetic metabolic engineering, xanthophyll synthesis by the metabolic engineering of model microorganisms shows great application potential. At present, compared to carotenes such as lycopene and β-carotene, xanthophyll has a relatively low production in engineering microorganisms due to its stronger inherent antioxidation, relatively high polarity, and longer metabolic pathway. This review comprehensively summarized the progress in xanthophyll synthesis by the metabolic engineering of model microorganisms, described strategies to improve xanthophyll production in detail, and proposed the current challenges and future efforts needed to build commercialized xanthophyll-producing microorganisms.