Objective: Biliary Tract Cancer (BTC) is a significant health concern with limited resectable cases. This meta-analysis assessed the safety of triplet regimens for advanced BTC, specifically gemcitabine, cisplatin, nab-paclitaxel, and gemcitabine, oxaliplatin, erlotinib, along with their associated adverse events. Method: Following PRISMA guidelines, we systematically reviewed PubMed/Medline, Google Scholar, and the Cochrane Library from inception to November 2022. Results: Our analysis of 5 studies favored Gem+Cisplatin+nab-Paclitaxel over GEMOX-T in terms of safety and adverse events. Qualitative analysis of 7 studies (491 patients) showed that Gem+Cisplatin+nab-Paclitaxel also outperformed in median overall survival, progression-free survival, and response rates. Conclusion: This study suggests that Gem+Cisplatin+nab-Paclitaxel is a safer and more effective treatment than GEMOX-T for advanced BTC. It exhibits superior outcomes in terms of survival and response rates. Further research should focus on optimizing treatment regimens to reduce adverse effects in advanced BTC patients.