Background: Frailty has been associated with increased mortality among hepatobiliary pancreatic (HBP) cancer patients. Nevertheless, estimates of frailty prevalence in HBP cancers and the precise average effect regarding mortality remains uncertain. The present systematic review and meta-analysis aimed to quantify: (1) the prevalence of frailty in patients with liver and pancreatic cancers and (2) the impact of frailty on mortality in patients affected by liver and pancreatic cancers. Methods: MEDLINE/PubMed database search was conducted from inception until 1 November 2021, the pooled prevalence and relative risk (RR) estimate were calculated. Results: A total of 34,276 patients were identified and the weighted prevalence of frailty was 39%; (95% [C.I.] 23–56; I2 = 99.9%, p < 0.0001). Frailty was significantly associated with increased mortality RR 1.98 (95% [C.I.] 1.49–2.63; I2 = 75.9%, p = 0.006). Conclusions: Frailty prevalence is common among HBP cancer patients and exerts a significant negative impact on survival. These findings are characterized by significant heterogeneity and caution is warranted on their interpretation. However, stratification of patients with HBP cancer by frailty status may provide prognostic information and may inform priorities for decision-making strategy.