Yeast has been well-used as a typical microbial platform to make fermented fine chemicals. However, various stress conditions severely restrict the production costs and benefits. One effective way to resolve such bottlenecks is to engineer transcription factors (TFs) to enhance strain tolerance and production efficiency through remodeling the transcript levels of different stress resistant genes. Here, we focus on the recent advances in the mechanisms of yeast adaptive responses upon stresses of heat, acetic acid and oxidants and classify them into different modules within yeast cells. In particular, novel strategies for the enhancement of both tolerance and yield by TFs engineering are examined. In addition, the applications of artificial transcription factor (ATFs)-based fabricating in metabolic fluxes optimization and quantitative evaluation are discussed. Lastly, we discuss challenges and potential solutions in exploiting TFs engineering and for A bio-based economy products.