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<div> Background Gallbladder cancer (GBC) is a rare, highly fatal disease with diagnosis in advanced stage and low survival rate. Nepal ranked 4^th position with highest rates of GBC for 10 countries in 2020. Objective To find the association between socio-demographic, behavioral and environmental factors associated with the development of GBC. Method A case-control study was conducted in 2021/22 with newly diagnosed gallbladder cancer cases from three cancer-specialized hospitals and one tertiary (superspeciality) hospital. Controls were selected from the same tertiary hospital and one additional hospital providing services to gallbladder pathologies for a huge population, making a total of five hospitals involved in the study. The ratio of cases to control was 1:1. The data collection was done through telephonic interviews using structured questionnaires. The risk factors for GBC were assessed by using unconditional logistic regression to find odds ratios and 95% confidence level for bivariate and multivariate analysis. The statistical analysis was carried out in STATA 18. Result A total of 240 respondents were enrolled in the study, among them half were GBC patients (cases) and half were gallbladder patients (controls). The average age of the respondents was 54.82±12.3 years, with female preponderance among both groups. On multivariate analysis, the risk factors studied were; parity ≥3 (AOR = 2.80, 95% CI: 1.17–6.66, P value 0.020), being ethnic group of Terai/Madhesi (AOR = 7.88, 95% CI: 3.16–19.66, P value <0.001), being Janajati (AOR = 3.36, 95% CI: 1.17–6.61, P value <0.001), having gallbladder related disease (AOR = 2.00, 95% CI:1.00–4.02, P value 0.049), consuming alcohol ≥100ml/day (AOR = 3.44, 95% CI:1.11–10.63, P value 0.032), exposed with pesticides ≥2 times in a year (AOR = 4.04, 95% CI: 1.27–12.89, P value 0.018) and consuming less vegetables and fruits (<1 times per day in a week) (AOR = 2.69, 95% CI:1.34–5.40, P value 0.005). Conclusion The study reveals key GBC risk factors, offering vital insights for targeted screening, resource allocation, and public health measures to mitigate risks in Nepal. </div>