Background Pelvic organ prolapse (POP) represents a major global health challenge for women. This study systematically analyzed the global disease burden of POP and associated risk factors from 1990 to 2021, including projections of future trends. Methods The data were derived from the GBD 2021 database and genome-wide association studies (GWAS). Additionally, we combined the age-period-cohort (APC) model with the autoregressive integrated moving average (ARIMA) model to analyze the driving factors and project future disease burden trends. Furthermore, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal relationships between risk factors and POP. Results From 1990 to 2021, the global crude incidence, prevalence, and disability-adjusted life years (DALYs) of POP increased by 66.2%, 68.7%, and 67.5%, respectively. However, in 2021, the global age-standardized disability rate (ASDR) of POP was 18.4% lower than in 1990. Notably, regions with a low sociodemographic index (SDI) exhibited a statistically significant elevation in disease burden. Furthermore, obese populations had a higher risk of developing POP, while those with higher education levels had a lower risk. According to the ARIMA model, global POP cases are projected to reach 148 million by 2036, while the age-standardized prevalence rate (ASPR) and ASDR are expected to decline further by 10.8% and 18.4%, respectively. Conclusion Aging population and socioeconomic inequality will further aggravate the disease burden of POP. To reduce the disease impact, future efforts should focus on strengthening global monitoring, optimizing medical resource allocation, and implementing targeted prevention and control strategies for high-risk populations.