Precipitation isotopes are widely used as hydroclimate proxies. However, limited understanding of the physical processes controlling their variability, particularly in the tropics, continues to constrain their reliable application. Here we examined spatial-temporal variations of precipitation isotopes across Southeast Asia by comparing observational data with simulations from isotope-enabled GISS ModelE2.1. We found a progressive decline in precipitation δ¹⁸O along monsoon tracks during the Northeast and Southwest monsoons, which reflects the dominant influence of large-scale monsoonal circulation. We further quantified the relative influences of local and regional processes on precipitation isotopes. We found that upstream rainout is the primary driver of seasonal precipitation δ¹⁸O variations, explaining ~39% – 48% of the seasonal δ¹⁸O range, followed by the isotopic composition of source vapor. These findings suggest that regional atmospheric processes, including large-scale convection in both source regions and along transport trajectories, govern precipitation isotopes in Southeast Asia. Moreover, the spatially heterogeneous responses of precipitation δ¹⁸O to major climate modes, such as the El Niño–Southern Oscillation and the Indian Ocean Dipole, indicate that different regions are predominantly influenced by distinct climate drivers.