Makawanpur district in Central Nepal, recognized as a national biodiversity hotspot, harbors a rich diversity of wild vegetables that significantly contribute to local nutrition and food security. However, declining abundance and usage of these species underscore the need for targeted domestication and cultivation efforts. This study surveyed wild vegetable species across three agro-climatic zones (500–2,200 masl) within varied land-use systems including forests, homegardens, fallow lands, and markets. Data on local plant names, edible parts, seasonal availability, consumption modes, primary users, and preference rankings were gathered through forest and field walks and semi-structured interviews with 144 respondents representing three ethnic groups. A prioritization framework based on nine variables—such as taste and sale preference, presence in homegardens, cultural use, ecological distribution, harvest seasonality, perceived threat, children’s preference, and processing potential—was applied to rank species for domestication potential. In total, 89 wild vegetable species were recorded, with forests and fallows identified as primary collection sites. Most species were consumed domestically, and only 26 were sold commercially. Knowledge of wild vegetables was significantly influenced by ethnicity, age, and altitude, but not by gender. Six species emerged as top domestication candidates: Bauhinia variegata, Dendrocalamus hamiltonii, Bambusa tulda, Diplazium esculentum, Dryopteris cochleata, and Tectaria gemmifera. The prioritization approach was effective, yet future refinements should incorporate additional variables like nutritional profiles and market viability to enhance the selection process. These findings offer a strategic foundation for promoting sustainable use and conservation of wild vegetable biodiversity in Nepal.