Against the backdrop of global climate change and rapid urbanization, understanding the spatiotemporal dynamics and driving mechanisms of vegetation net primary productivity (NPP) is critical for ensuring regional ecological security and achieving carbon neutrality goals. This study focuses on the Yangtze River Delta Urban Agglomeration (YRDUA) and integrates multi-source remote sensing data with socioeconomic statistics. By combining interpretable machine learning (XGBoost-SHAP) with multiscale geographically weighted regression (MGWR), and incorporating Theil–Sen trend analysis and Mann–Kendall significance testing, we systematically analyze the spatiotemporal variations in NPP and its multiscale driving mechanisms from 2001 to 2020. The results reveal the following: (1) Total NPP in the YRDUA shows an increasing trend, with approximately 24.83% of the region experiencing a significant rise and only 2.75% showing a significant decline, indicating continuous improvement in regional ecological conditions. (2) Land use change resulted in a net NPP loss of 2.67 TgC, yet ecological restoration and advances in agricultural technology effectively mitigated negative impacts and became the main contributors to NPP growth. (3) The results from XGBoost and MGWR are complementary, highlighting the scale-dependent effects of driving factors—at the regional scale, natural factors such as elevation (DEM), precipitation (PRE), and vegetation cover (VFC) have positive impacts on NPP, while the human footprint (HF) generally exerts a negative effect. However, in certain areas, a dose–response effect is observed, in which moderate human intervention can enhance ecological functions. (4) The spatial heterogeneity of NPP is mainly driven by nonlinear interactions between natural and anthropogenic factors. Notably, the interaction between DEM and climatic variables exhibits threshold responses and a “spatial gradient–factor interaction” mechanism, where the same driver may have opposite effects under different geomorphic conditions. Therefore, a well-balanced combination of land use transformation and ecological conservation policies is crucial for enhancing regional ecological functions and NPP. These findings provide scientific support for ecological management and the formulation of sustainable development strategies in urban agglomerations.
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