Thermostability is an essential requirement of enzymes in the industrial processes to catalyze the reactions at high temperatures; thus, enzyme engineering through directed evolution, semi-rational design and rational design are commonly employed to construct desired thermostable mutants. Several strategies are implemented to fulfill enzymes' thermostability demand including decreasing the entropy of the unfolded state through substitutions Gly → Xxx or Xxx → Pro, hydrogen bond, salt bridge, introducing two different simultaneous interactions through single mutant, hydrophobic interaction, filling the hydrophobic cavity core, decreasing surface hydrophobicity, truncating loop, aromatic-aromatic interaction and introducing positively charged residues to enzyme surface. In the current review, horizons about compatibility between secondary structures and substitutions at preferable structural positions to generate the most desirable thermostability in industrial enzymes are broadened. KEY POINTS: • Protein engineering is a powerful tool for generating thermostable industrial enzymes. • Directed evolution and rational design are practical approaches in enzyme engineering. • Substitutions in preferable structural positions can increase thermostability.