The development of biorefineries directed to the production of fuels, chemicals, and energy is important to reduce economic dependence and environmental impacts of a petroleum‐based economy. The last two decades have witnessed a fast industrialization and the surge in the energy demands that has compelled the energy sector to think beyond fossil fuels. The energy crisis and the need for a sustainable environment development shifted the energy spectrum toward biomass‐based renewable energy generation. Alternate fuels like lignocellulosic ethanol can be produced and used for blending in gasoline and other applications for sustainable development. Saccharomyces sp. has been a fascinating yeast for fermentation processes since Ancient Greece, where it was used for wine making. There are several technical challenges with commonly used Saccharomyces sp. including: (i) does not convert pentose sugars; (ii) has low tolerance to alcohols, acids, and solvents; (iii) is very sensitive to inhibitors (e.g., furfural, 5‐hydroxymethylfurfural, aromatics, etc.) generated during hydrolysis of agrowastes; and (iv) has fermentative stresses (e.g., pH). These limitations obstruct the process when agro‐waste is used as a feedstock for biofuel production. These challenges can be overcome by taking systems approaches using state‐of‐the‐art tools of systems biology, synthetic biology, and evolutionary engineering in the context of industrial bioprocess along with strain adaptation strategies. This chapter focuses on recent developments of yeast biotechnology by strain adaptation and strain development.