Speleothem oxygen isotopes provide key insights into Holocene monsoon variability, but the scale-dependent and regionally variable controls on precipitation <em>&delta;</em>¹⁸O remain poorly resolved. Here, we use a continuous 8.3 ka isotope-enabled transient simulation based on AWI-ESM2-wiso to investigate Holocene climatic and isotopic changes and quantify driving mechanisms for the isotopic variations via a four-predictor multiple linear regression (MLR) model. The simulation successfully reproduces the orbitally driven long-term weakening of Northern Hemisphere monsoons and the bipolar hydroclimatic response to the 8.2 ka freshwater perturbation, characterized by a southward Intertropical Convergence Zone (ITCZ) shift, Northern Hemisphere drying and isotopic enrichment, and Southern Hemisphere moistening and depletion. MLR results show that regional precipitation amount serves as the dominant and temporally stable control on monsoon <em>&delta;</em>¹⁸O. Secondary predictors including moisture transport, continental recycling, and source temperature exert regionally divergent and time-varying influences. Supplementary large-scale climate indices can improve model performance for specific monsoon domains. El Ni&ntilde;o und die Southern Oscillation (ENSO) is the most widespread teleconnection affecting most monsoon domains, while Atlantic Meridional Overturning Circulation (AMOC) and South Atlantic Convergence Zone (SACZ) act as additional key controls over Southwestern South American Monsoon. Spatial correlation analyses further demonstrate that the precipitation amount effect is weak and spatially heterogeneous at local grid scales but becomes robust and uniform at the regional scale. This further indicates that individual speleothem records may misrepresent large-scale monsoon signals due to local spatial noise, while regional proxy ensembles effectively capture the dominant precipitation-isotope relationship.