Dragon fruit (Hylocereus spp.), a tropical cactus species, has gained global recognition for its exceptional adaptability to arid environments, high nutritional value, and emerging therapeutic potential. This review presents an integrated and up-to-date synthesis of recent advancements in agronomic practices, postharvest handling technologies, and biomedical research related to dragon fruit. Agronomic improvements such as high-density planting, drip fertigation, organic nutrient management, biostimulant use, and artificial flower induction have been shown to enhance yield, fruit quality, and resource efficiency under diverse agro-climatic conditions. Postharvest strategies including cold storage, modified atmosphere packaging, edible coatings, and non-thermal techniques such as cold plasma treatment are critically evaluated for their effectiveness in maintaining physicochemical quality, reducing microbial spoilage, and preserving important bioactive compounds during storage and transport. The review also examines the comprehensive nutritional profile, emphasizing its content of dietary fiber, vitamins, minerals, betalains, and phenolics, which contribute to its antioxidant, antidiabetic, and anticancer properties. In addition, recent molecular docking studies are summarized, revealing the potential of major phytopigments such as betacyanin and betaxanthin to interact with therapeutic targets like DNA topoisomerase I, cyclin-dependent kinase 6 (CDK6), alpha-amylase, and lysosomal acid alpha-glucosidase, suggesting possible applications in functional food development and pharmaceutical research. By bridging advancements in cultivation, postharvest preservation, and bioactivity research, this review provides a comprehensive foundation for future scientific inquiry, value addition, and sustainable commercialization of dragon fruit. Despite these advancements, challenges such as inconsistent cultivation practices, limited postharvest technologies, and the need for clinic