Background: Patients with biliary tract cancers (BTC) are typically diagnosed at late stage, with limited treatment options. As such, BTC is associated with poor prognosis, high economic burden and reduced health-related quality of life (HRQoL). As the treatment paradigm is evolving, with multiple immunotherapies showing promise, this study aimed to assess the current disease and treatment landscape. Methods: Systematic literature reviews (Embase, MEDLINE, Cochrane, NHS-EED; database inception to Feb 10, 2023) were conducted for HRQoL and economic burden. Targeted literature reviews (Embase, MEDLINE) were conducted for epidemiology (Jan 01 2017–Feb 06 2023) and treatment guidelines/patterns (Jan 01 2012–Feb 06 2023). Conference abstracts were also searched (2019–2022). Eligibility criteria included global studies (English language) in adults with metastatic and/or unresectable BTC. Results: Overall, 264 studies were included (epidemiology=170, treatment guidelines=14, treatment patterns=50, HRQoL=12, economic burden=18). In the US, Europe and Asia, age-standardized incidence rates were 5.04, 8.39–8.78 and 9.1–10.1 (per 100,000 person-years) and prevalence rates were 0.01%, 0.02–0.34% and 0.02–2.61%, respectively. Treatment pattern studies were mainly from Asia, Europe (n=19 each) and North America (n=10). Gemcitabine [gem]-based chemotherapy was most common in 1L BTC (24–100%) and fluorouracil-based regimens were common in 2L+ BTC (12.3–74.3%). Median overall survival (mOS) for gem-based and fluorouracil-based 1L regimens were 7.7–14.8 months and 7–16.7 months, respectively. Disease progression/toxicity frequently led to treatment discontinuation/dose modifications. In the US, use of non-guideline-based regimens increased by line of therapy (LOT). Among the clinical studies (n=5) reporting HRQoL in 1L, n=4 assessed gem-based combinations. BTC impaired HRQoL domains for anxiety, tiredness (EORTC QLQ-BIL21), work productivity, activity impairment (WPAI scale) and depression (PHQ-9). BTC was associated with substantial economic burden. Mean total all-cause healthcare costs per patient per month (PPPM) increased by LOT (US; 1L: $19,589–25,517, 2L: $22,617–29,721, 3L: $23,256–33,534). US healthcare resource utilization in 1L was driven by outpatient visits (98%), emergency department visits (33–80%) and hospitalization (70–80%). Mean hospital stay ranged from 0.6–7 days PPPM. Conclusions: Epidemiology data varied between Western and Asian populations, but gem-based chemotherapy was identified as the standard of care across regions. There is high unmet need in advanced BTC, as existing options are characterized by poor survival outcomes and considerable economic burden. These findings indicate a need for novel approaches for the management of BTC.