<p>Spine gourd (<i>Momordica dioica</i> Roxb<i>.</i>), a dioecious and underutilized cucurbit, is increasingly recognized for its nutritional richness, medicinal potential, and adaptability to marginal agroecosystems. Traditionally cultivated in South Asia, particularly by tribal communities, spine gourd has gained scientific attention due to its high content of carotenoids, vitamins, minerals, and bioactive compounds such as flavonoids, saponins, and triterpenoids. These constituents contribute to its anti-diabetic, anti-inflammatory, antioxidant, and antimicrobial properties. Despite its promise, spine gourd remains an orphan crop with limited systematic breeding, largely due to its constraints in compiling reproductive biology, propagation problems, and poor genetic characterization. Challenges such as asynchronous flowering, seed dormancy, low commercial awareness, and inadequate conservation efforts continue to hinder large-scale adoption. Recent advances, including mutation breeding for inducing hermaphroditism, identification of sex-linked molecular markers, and emerging genome-enabled approaches, are mitigating these barriers and accelerating cultivar development. The review examines its taxonomy, phylogeny, botanical traits, genetic resources, and historical breeding efforts, highlighting its potential for improvement through selection, hybridization, and molecular tools. Nevertheless, integration of wild relatives, next-generation phenotyping, and participatory breeding offer strategic opportunities for enhancing yield, fruit quality, and stress resilience. The paper also discusses future prospects in nutraceuticals, sustainable agriculture, emphasizing the need for multidisciplinary efforts to unlock the full potential of spine gourd.</p>