This study examines the global burden of pancreatic cancer from 1990 to 2021 and projects future trends, aiming to provide insights for health policy and resource allocation to mitigate the disease’s impact. We assessed the pancreatic cancer burden globally and by subgroups, employing linear regression models to analyze trends from 1990 to 2021. Cluster analysis was used to evaluate burden patterns across Global Burden of Disease regions. Forecasting was conducted using the age-period-cohort model and its Bayesian variant. Additionally, we evaluated risk factor contributions to the pancreatic cancer burden and used frontier analysis to explore the relationship between sociodemographic advancements and cancer rates. In 2021, pancreatic cancer accounted for 508 533 new cases, 439 001 prevalent cases, 505 752 deaths, and 11 316 963 disability-adjusted life years (DALYs). High-risk groups included males and middle-aged to older adults, with high-risk areas identified in regions with higher sociodemographic index (SDI). From 1990 to 2021, both pancreatic cancer cases and age-standardized rates (ASR) increased. Notably, high fasting plasma glucose surpassed tobacco as a leading risk factor for pancreatic cancer. Frontier analysis revealed an inverse relationship between SDI and pancreatic cancer ASR, plateauing at an SDI of 0.60. The global burden of pancreatic cancer continues to rise, with significant disparities across demographic and geographic segments. These findings highlight the need for targeted interventions and resource allocations to address this growing public health challenge.