In the last few decades, there has been a rapid increase in the discovery of drugs from natural products, particularly secondary metabolites. Various efforts have been undertaken to enhance and optimize the production system of these secondary metabolites to meet the increasing global market demand. Recently, metabolic engineering has been used for the heterologous synthesis of secondary metabolites in the engineered yeast strains. Here, we highlight the recent advancements in the production of pharmaceutically important secondary metabolites in metabolically engineered yeast, such as Saccharomyces cerevisiae and Pichia pastoris. Furthermore, we also emphasize the important application of synthetic biology methods that are supported by state-of-the-art post-genomic tools to improve the efficiency and success rate of yeast metabolic engineering for the production of natural drugs. Metabolic engineering using yeast as a microbial host factory to produce pharmaceutically useful secondary metabolites is a very promising strategy, which can be used to support the industrial production system.