Brain and central nervous system (CNS) cancers present significant health challenges globally, characterized by increasing incidence and mortality rates. This study utilizes data from the Global Burden of Disease (GBD) 2021 to analyze trends and project future burdens.We calculated age-standardized rates (ASRs) of incidence, mortality, and disability-adjusted life years (DALYs) for brain and CNS cancers from 1990 to 2021. Trends were analyzed using estimated annual percentage change, and future projections were made with an Autoregressive Integrated Moving Average (ARIMA) model. Correlations between the socio-demographic index (SDI) and ASR were also examined.The study revealed a 106% increase in incidence and a 63.67% rise in deaths over the study period. The ARIMA model predicts declines in incidence, mortality, and DALYs by 2040. Higher incidence rates were observed in high SDI regions, while greater mortality occurred in low SDI areas, indicating significant disparities.These findings underscore the need for targeted interventions and sustained healthcare investments to manage the global burden of brain and CNS cancers effectively. The projected declines suggest potential effectiveness of current public health strategies but highlight the importance of addressing socio-demographic disparities.Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.