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Background Gastroesophageal reflux disease (GERD) and asthma often co-occur, yet their joint trajectories and shared drivers may differ across regions. Methods Using Global Burden of Disease (GBD) 2023 estimates (1994–2023), we compared East Asia, Tropical Latin America, and High-income North America. Age-specific associations were assessed by Spearman correlation. Trends were quantified with Joinpoint regression (AAPC) and forecasts (2024–2033) generated using ETS/ARIMA. Shared drivers were screened using Random Forest with SHAP. Associations between exposures and disease burden were quantified using negative binomial regression of prevalence counts with a log(population) offset, and geographic heterogeneity tested using exposure × region interaction models. Granger causality and multigroup structural equation modelling (SEM) were used to explore temporal directionality and pathways. Results In 2023, GERD age-standardised prevalence was highest in Tropical Latin America (16,591 per 100,000) and lowest in East Asia (4,465 per 100,000), yet East Asia carried 84.6 million GERD cases. Trends showed increasing GERD and asthma in East Asia, rising asthma in Tropical Latin America, and declining GERD but increasing asthma in High-income North America. In pooled models, asthma was positively associated with diet high in red meat (RR 1.66, 95% CI 1.51–1.84), diet low in vegetables (1.56, 1.11–2.20), high fasting plasma glucose (1.13, 1.08–1.19), low physical activity (1.16, 1.02–1.33), and suboptimal breastfeeding (1.36, 1.23–1.52). GERD was positively associated with sugar-sweetened beverages (1.51, 1.25–1.82), suboptimal breastfeeding (1.34, 1.27–1.42), and high fasting plasma glucose (1.03, 1.00–1.06). Interaction models indicated strong regional effect modification, with fasting glucose positively associated with asthma in East Asia (1.23, 1.18–1.28) and Tropical Latin America (1.16, 1.14–1.19) but inversely in High-income North America (0.97, 0.95–0.99). Conclusion GERD–asthma comorbidity follows distinct regional trajectories, and shared metabolic/lifestyle drivers show marked geographic heterogeneity, supporting context-specific prevention strategies.