The traditional chemical manufacturing based on petroleum as raw material has had profound impacts in the development of modern society. However, it also has many drawbacks, such as environmental pollution and lack of sustainability. In contrast, biomanufacture with microorganisms as industrial chassis is gradually becoming a hot spot in industrial production due to its advantages of environmental friendliness and sustainability. Nonetheless, the limitations of traditional industrial biotechnology, including susceptibility to microbial contamination, complex fermentation processes, and difficulties in achieving continuous fermentations, have hindered the competitiveness of their products in terms of production costs compared to chemical industries To address these challenges, “Next Generation Industrial Biotechnology” (NGIB) with extremophiles as non-conventional chassis, has been undergoing continuous development with increasing global attentions.The basis of NGIB is extremophiles, such as halophiles, acidophiles, and thermophiles, known for their ability to thrive in extreme environments. Through molecular engineering of extremophiles, especially Halomonas spp., the recombinants can utilize various inexpensive carbon sources for continuous open fermentation, leading to the production of diverse high-value products with reduced cost. This review defines and summarizes the characteristics of extremophiles, highlighting their ability to grow rapidly in extreme environments like high salt, high temperature, and extreme pH. Subsequently, the review summarizes current genetic engineering approaches for extremophiles, such as promoter engineering, CRISPR-based gene editing, community fate strategy, and stable plasmid vectors. Additionally, metabolic engineering methods such as precursor supplementation, pathway disruption, byproduct reduction, and enhanced transport are discussed, along with various products including PHA, proteins, amino acids, and small molecule derivatives. The review also identifies challenges in extremophile engineering, such as the lack of suitable plasmid vectors, low plasmid transformation efficiency, lack of efficient gene editing tools, and long growth and fermentation cycle, but proposes corresponding solutions. Finally, the review proposes leveraging the characteristics of different types of extremophiles to produce advantageous products, thereby driving the development of next generation industrial biotechnology based on various extremphiles, and achieving green, environmentally friendly, and sustainable biomanufacturing.