Thermozymes (from thermophiles or hyperthermophiles) offer obvious advantages due to their excellent thermostability, broad pH adaptation, and hydrolysis ability, resulting in diverse industrial applications including food, paper, and textile processing, biofuel production. However, natural thermozymes with low yield and poor adaptability severely hinder their large-scale applications. Extensive studies demonstrated that using genetic modifications such as directed evolution, semi-rational design, and rational design, expression regulations and chemical modifications effectively improved enzyme's yield, thermostability and catalytic efficiency. However, mechanism-based techniques for thermozymes improvements and applications need more attention. In this review, stabilizing mechanisms of thermozymes are summarized for thermozymes improvements, and these improved thermozymes eventually have large-scale industrial applications.