We aimed to estimate the cost of snakebite and its impact on the economy of snakebite-affected households in southern Nepal. We conducted cross-sectional and prospective studies of confirmed snakebite cases at two hospitals in south central and southwestern Nepal during May to October 2020. We estimated the economic impact of snakebite on affected households by evaluating direct and indirect costs for treatments and opportunity costs of patients and attendants (household members or relatives). We included 553 snakebites that caused 185 envenomings (34%), resulting in 15 deaths (case fatality rate, 8%). These occurred across 87 subdistricts, 21 districts, and six provinces (25% rural, 75% urban overall). Median direct, indirect, and opportunity costs of snakebite were US$95.30, US$65.80, and US$4,995.20 for envenomings and US$14.50, US$13.50, and US$10.10 for nonenvenomed snakebites, respectively. The impact of snakebite envenomings on household economy included not only the remarkable out-of-pocket expenditure but also the loss of patients' and visitors' productivity (i.e., daily income/wages while seeking snakebite care in hospitals). Lack of insurance for snakebite treatment increased the psychosocial and economic burden. Deterioration in family economy and psychology was particularly severe when death from snakebite affected breadwinners. Therefore, taking action to minimize the impact of snakebite envenoming becomes a priority for all.