<p>Lipases are versatile enzymes with widespread industrial applications, including detergents, food processing, pharmaceuticals, biofuels, and environmental cleanup. Their ability to catalyze both hydrolytic and synthetic reactions under diverse conditions underpins their biotechnological significance. Native lipases, however, exhibit limitations such as low stability, narrow substrate spectrum, and low production yields, which limit their large-scale application. Emerging developments in genetic and protein engineering have enabled accurate modulation of enzyme properties and expression systems, offering potential solutions to overcome these challenges. This review presents an integrated view of existing strategies for designing high-performance lipases for industrial applications. It summarizes advancements from metagenomic discovery and gene optimization to expression optimization through codon improvement, promoter adjustment, signal peptide design, and chaperone-mediated folding. Protein engineering strategies, including rational design, directed evolution, and domain recombination; are addressed to enhance catalytic activity, selectivity, and thermostability. Concomitantly, breakthroughs in fermentation optimization, host metabolism engineering, and enzyme immobilization have enhanced the scalability and operational robustness of lipase manufacturing. Novel omics-driven and systems biology platforms now facilitate the rational design of microbial hosts optimized for efficient enzyme biosynthesis. Collectively, these advances outline a coherent blueprint for engineering lipases into strong, industrially applicable biocatalysts.</p> Graphical abstract <p></p>