Cucurbits, members of the Cucurbitaceae family, are globally significant horticultural crops valued for their commercial and nutritional benefits. Key crops include watermelon, cucumber, melon, pumpkin, and various gourds. According to FAOSTAT (2023) and DAFW (2023–24), the total global cucurbit production was approximately 251.8 million tonnes with a global trade value of about US $6.9 billion, while India’s cucurbit production was around 13.4 million tonnes. These crops exhibit wide genetic diversity due to their cross-pollinated nature and long history of cultivation. Recent advances in biotechnology, including gene editing and transgenic tools, have accelerated breeding efforts, enabling trait improvement and the development of stress-resilient cultivars. Integration of genomics with proteomics and metabolomics is fostering a systems biology approach, enhancing the efficiency of breeding strategies. Use of molecular markers in marker-assisted selection has allowed for high-quality and nutritionally improved cucurbit varieties to be produced. To address climate change problems, nutritional security, and sustainable agriculture, the potential of genomic tools for cucurbit breeding in the future is clear. This review article focuses on constraints in cucurbit cultivation, genetic transformation, CRISPR genome editing, hybridization, and speed breeding; QTL mapping in cucurbits; molecular markers for biotic and abiotic stress tolerance; modern transgenic approaches; high-throughput phenotyping; and recent genomic advances for crop improvement in cucurbits.