AbstractWith the rapid development of systems and synthetic biology, the non-model bacteria, Halomonas spp., have been developed recently to become a cost-competitive platform for producing a variety of products including polyesters, chemicals and proteins owing to their contamination resistance and ability of high cell density growth at alkaline pH and high salt concentration. These salt-loving microbes can partially solve the challenges of current industrial biotechnology (CIB) which requires high energy-consuming sterilization to prevent contamination as CIB is based on traditional chassis, typically, Escherichia coli, Bacillus subtilis, Pseudomonas putida and Corynebacterium glutamicum. The advantages and current status of Halomonas spp. including their molecular biology and metabolic engineering approaches as well as their applications are reviewed here. Moreover, a systematic strain engineering streamline, including product-based host development, genetic parts mining, static and dynamic optimization of modularized pathways and bioprocess-inspired cell engineering are summarized. All of these developments result in the term called next-generation industrial biotechnology (NGIB). Increasing efforts are made to develop their versatile cell factories powered by synthetic biology to demonstrate a new biomanufacturing strategy under open and continuous processes with significant cost-reduction on process complexity, energy, substrates and fresh water consumption.