The blue crab, Callinectes sapidus (Rathbun, 1896), has become an invading species in the Mediterranean region, almost completely replacing native species within a few years and causing significant loss to local production. In some areas, there is an urgent need to propose new supply chains based on blue crab exploitation, where the potential valorisation routes for unsaleable blue crab and waste play an important role. The final purpose is to transform a threat into a treasure, towards a more sustainable world. In addition to applications in food industries, the considerable quantity of bioactive compounds in by-products, such as polysaccharides, proteins, amino acids, carotenoids, and chitin, needs to be capitalised by means of efficacious strategies and appropriate management. Crab exoskeleton can also be exploited as a carbonaceous material with applications in several fields, including medicine. Blue crab bioactive molecules have been widely recognised for having antioxidant, anticancer, antidiabetic, anti-inflammatory, and antimicrobial properties. Due to these functional and distinctive activities, such high-value components could be employed in various industries such as food–feed–pharma and cosmetics. Recycling and reusing these underutilised but economically valuable waste or by-products could help to reduce the environmental impacts of the whole supply chain from the perspective of the circular economy.