Beekeeping contributes to poverty reduction in many developing countries, and in addition, provides pollination services for sustainable crop production. In Nepal, management practices associated with beekeeping are poorly characterized, and so the potential for this sector to further contribute to livelihood development remains unclear. This study sought to examine and identify factors associated with production efficiency and financial profitability of beekeeping with the aim of enhancing economic gains for Nepali beekeepers. Our study included a sample of 150 respondents from more than twenty commercial beekeeping districts across the Terai and mountainous regions of Nepal. Profitability of beekeeping with the European honeybee (Apis mellifera) Linnaeus, 1758 (Hymenoptera: Apidae) and the Asian honeybee Apis cerana Fabricius, 1793 (Hymenoptera: Apidae) was quantified and disaggregated according to several variables, including hive-derived products produced, marketing strategy employed, number of beehives managed, and postharvest management practices. Our results showed that the different types of management practices adopted (such as number of beehives kept, colony multiplication, supplementary feeding, month of honey harvesting, and marketing approach) significantly influenced the productivity and economic profitability of beekeeping. Our results also revealed that professional supports, such as the availability of subsidies and training, were key factors to enhance productivity. As a whole, this study provides insight into the biological factors and management practices associated with higher economic returns from beekeeping. This work can help guide policymakers and professional support agencies to expand commercial beekeeping for sustainable livelihood development in Nepal and beyond.