Agricultural diversification and high-quality products deriving from sustainable crops such as hemp can represent a solution to revitalize marginal areas and reverse land abandonment. This study aimed at comparing four different hemp cultivars (Carmagnola Selezionata, "CS"; Futura 75, "FUT"; Felina 32, "FEL"; Secuieni Jubileu, "JUB") to provide information to select the best suited cultivar for cultivation in mountain marginal areas and for specific end-use applications. Hemp cultivars were cultivated in a single experimental field to compare their ecological and agronomic behavior (duration of life cycle phases, plant size and biomass allocation, and plant resource-use strategies). Through metabolomic analysis of both vegetative and reproductive parts of the plants we tested the presence of substances of nutraceutical interest and traced seed nutritional profile. The four cultivars had different ecological and agronomic behavior, and nutritional profile. We found several compounds with potential pharmaceutical and nutraceutical values in all parts of the plant (leaves, inflorescences, and stems). JUB resulted the most suitable for seed production while CS showed the highest content of bioactive compounds in flowers and leaves. FUT, showed the best suitability for multi-purpose cultivation, while FEL seemed to be not appropriate for the cultivation in mountain area. The multi-disciplinary approach we adopted was effective in distinguish across hemp cultivars and provided information to farmers for the selection of the best hemp cultivar to select. Hemp had a high potential for cultivation in marginal lands, demonstrating to be an economic resource due to its multi-purpose use and to the possibility to generate high-added values products. Our results could serve as a stimulus for the reintroduction of this culture in the study area and in other similar environments.