Cucurbitaceae family contains important economic and medical crops, they can be divided into two categories according to the worldwide consumption, use, and production. The Cucurbit Popular Crops (CuPoC) are comprised of cucumber, the Cucurbita group (pumpkin and squash), melon and watermelon. On the other hand, Neglected and Underutilized Cucurbit Species (NUCuS) group has been used as food sources, medicinal properties and elements in the elaboration of different types of items. The NUCuS is represented in this review work by bitter gourd, bottle gourd, chayote, ridge gourd, and snake gourd, which are recognized mainly in Asia. The center of origin of the majority of NUCuS was proposed to be in the Old World. In contrast, the origin of chayote or Sechiumedule (Jacq.) Sw. was suggested in the New World, precisely in Mesoamerican region based on linguistic uses and distribution of wild relatives. The environmental factors along with artificial selection, production systems and traditional knowledge have been influenced the evolutionary history of NUCuS, Infraspecific variation of chayote has been reported in Mexico over-described varietal groups. These descriptors were determined based on biochemical and morpho-structural traits; however, cytogenetic analyses are scarce. Specifically, chromosome and nuclear content analyses are important to support botanical groups, analyze artificial selection history, developing breeding and conservation programs. The present review paper discusses agronomic and evolutionary importance based on cytological evidence in NUCuS, mainly in the prominent chayote; with the perspective to prompt breeding, conservation, cytology, structural and functional genomics research for its sustainable utilization.