Melon grafting represent an increasingly important strategy against biotic and abiotic stresses. Cucurbita hybrid rootstocks have been extensively developed for this purpose, but it is necessary to find new alternatives. In this work, several experimental rootstocks of cultivated and wild resources from the Cucurbita and Cucumis genera have been evaluated using Piel de Sapo melon as scion. Cucurbita rootstocks tended to increase fruit size and seed cavity and offered more rounded shapes at the early stages of ripening, but this effect was later minimised. Cucumis rootstocks tended to show less vigour than those of Cucurbita. C. metuliferus hybrid rootstock caused plant collapse at specific environmental conditions, probably due to differences in the growth of rootstock and scion. One of the Cucurbita maxima x C. moschata and the Cucurbita pepo experimental hybrids were also less vigorous, delaying flowering and fruit set, and compromising yield. The effects of Cucurbita and Cucumis rootstocks on sugar and acid accumulation of Piel de Sapo were almost negligible, but they altered the volatile profile. This last impact depended on the specific scion x rootstock interaction and the environmental conditions. Cucumis rootstocks tended to minimise it, especially the hybrid Cucumis melo subsp. melo x C. melo subsp. agrestis Pat 81, which offered a volatile profile highly resembling the non-grafted control. Among Cucurbita alternatives, the commercial hybrid Cucurbita maxima x C moschata had the lowest impact, while other experimental hybrids C. moschata x C. moschata and C. maxima x C. moschata increased levels of alcohols. Among Cucumis rootstocks, the hybrids of wild species Cucumis ficifolius x C. anguria and C. ficifolius x C. myriocarpus, and C. metuliferus had a higher impact on the volatile profile.