Technical Abstract: Papayas are sweet, flavorful tropical fruit, rich in vitamin C and carotenoids. Multiple interactions among preharvest environmental conditions, genetics, and physiology determine papaya nutritional composition at harvest. Selecting a cultivar with the genetic potential for high nutrient content and choosing a production location with a favorable climate are essential to maximize the nutritional composition of papayas. The genetic diversity within Carica papaya is quite narrow, but it is possible to broaden the germplasm base to improve nutritional composition through traditional breeding or transgenic methods. Recent advances in papaya genomics, gene identification, transcript characterization, high-density linkage maps, and transgenic methods will support further germplasm improvement. Potential applications of the genetic tools for enhancing papaya nutritional composition are explored, with an emphasis on carotenoids and ascorbic acid.