Vegetation Net Primary Productivity (NPP) plays a crucial role in terrestrial carbon sinks and the global carbon cycle. Investigating the spatiotemporal dynamics and influencing factors in the Yangtze River Delta (YRD) region can furnish a solid scientific foundation for green, low-carbon, and sustainable development in China, as well as a reference for other rapidly urbanizing regions. This study focuses on the YRD region as an illustration and utilizes the Carnegie–Ames–Stanford Approach (CASA model) to quantify NPP in this region from 2000 to 2018. Investigation into the spatiotemporal dynamics and influencing factors was conducted using Theil–Sen median trend analysis and scenario analysis. The results indicate that the NPP in the YRD region from 2000 to 2018 exhibited pronounced spatial differentiation characteristics, typically exhibiting a spatial distribution pattern of being high in the south and low in the north, high in the west and low in the east. Additionally, the expansion of built-up areas and the reduction in cultivated land have the potential to reduce NPP in the YRD region. Moreover, the influence of land-use and land-cover change (LULCC) is anticipated to be relatively limited compared to that of climate change. Furthermore, changes in precipitation were found to be positively correlated with changes in NPP, with the effect being relatively more pronounced. The correlation between temperature and NPP demonstrated spatial differentiation, with a mainly positive correlation in the central and southern parts of the YRD and a mainly negative correlation in the northern part. Changes in solar radiation had a negative correlation with changes in NPP. Based on these results, it is recommended that local governments strictly enforce urban development boundaries and manage the disorderly expansion of built-up areas, enhance the regional irrigation infrastructure, and address air pollution, so as to ensure the necessary conditions for the growth of vegetation, reduce greenhouse gas emissions, and control regional temperature rises. This study can provide stronger evidence for revealing the influencing mechanisms of NPP through the control of impact conditions and the exclusion of confounding factors via scenario analysis. The policy implications can offer insights into NPP enhancement and environmental management for the YRD and other rapidly urbanizing regions.