Identification of rootstocks capable of improving the nitrogen use efficiency (NUE) of the scion could reduce N fertilization and nitrate leaching; however, screening different graft combinations under field conditions can be costly and time-consuming. This study evaluated a rapid and economical methodology for screening of melon rootstocks for NUE. Two experiments were designed. In the first, melon plants (Cucumis melo L. cv. Proteo) either ungrafted or grafted onto four commercial rootstocks: ‘Dinero’ and ‘Jador’ (Cucumis melo L.), ‘P360’, and ‘PS1313’ (Cucurbita maxima Duchesne × Cucurbita moschata Duchesne) grown in hydroponics were compared in terms of shoot dry biomass, leaf area, root-to-shoot ratio, SPAD index, shoot N uptake, and nitrate reductase (NR) activity at the early developmental stage in response to nitrate availability (0.5, 2.5, 5, 10, or 15 mm of NO3 –). The second experiment was aimed to confirm whether the use of a selected rootstock with high NUE (‘P360’) could improve crop performance and NUE of grafted melon plants under field conditions. In the first experiment, carried out under greenhouse conditions, melon plants grafted onto ‘Dinero’, ‘Jador’, and ‘P360’ rootstocks needed 5.7, 5.2, and 6.1 mm of NO3 –, respectively, to reach half-maximum shoot dry weight, whereas plants grafted onto ‘PS1313’ rootstock and the control treatment (ungrafted plants) needed 9.1 and 13.1 mm of NO3 –, respectively. Total leaf area, SPAD index, and shoot N uptake increased linearly and quadratically in response to an increase of the N concentration in the nutrient solution. At 2.5 mm of NO3 –, melon plants grafted onto both C. melo and Cucurbita maxima × Cucurbita moschata rootstocks had the highest NR activity, whereas no significant difference was observed at 10 mm of NO3 –. In the second experiment, carried out under open field conditions, increasing the N fertilization rates from 0 to 120 kg·ha−1 increased the total and marketable yields of melon plants, whereas the NUE decreased. When averaged over N levels, the marketable yield, NUE, and N uptake efficiency were higher by 9%, 11.8%, and 16.3%, respectively, in ‘Proteo’ grafted onto ‘P360’ than in ungrafted ‘Proteo’ plants.