Nervonic acid (NA) is a monounsaturated very long-chain fatty acid (VLCFA) and has been identified with critical biological functions in medical and health care for brain development and injury repair. Yet, the approaches to producing NA from the sources of plants or animals continue to pose challenges to meet increasing market demand, as they are generally associated with high costs, a lack of natural resources, a long life cycle, and low production efficiency. The recent technological advance in metabolic engineering allows us to precisely engineer oleaginous microbes to develop high-content NA-producing strains, which has the potential to provide a possible solution to produce NA on a commercial fermentation scale. In this Review, the biosynthetic pathway, natural sources, and metabolic engineering of NA are summarized. The strategies of metabolic engineering that could be adopted to modify oleaginous yeast to produce NA are discussed in detail, providing the prospecting views for the microbial cells producing NA.