Net primary productivity (NPP) is a core ecological indicator within terrestrial ecosystems, representing the potential of vegetation growth to offset anthropogenic carbon emissions. Thus, assessing NPP in a given region is crucial for promoting regional ecological restoration and sustainable development. This study utilized the CASA model and GEE to calculate the annual average NPP in Shandong Province (2001–2020). Through trend analysis, Moran’s Index, and PLS−SEM, the spatiotemporal evolution and driving factors of NPP were explored. The results show that: (1) From 2001 to 2020, NPP in Shandong showed an overall increasing trend, rising from 254.96 to 322.49 g C·m⁻²/year. This shift was accompanied by a gradual eastward movement of the NPP centroid, indicating significant spatial changes in vegetation productivity. (2) Regionally, 47.9% of Shandong experienced significant NPP improvement, 27.6% saw slight improvement, and 20.1% exhibited slight degradation, highlighting notable spatial heterogeneity. (3) Driver analysis showed that climatic factors positively influenced NPP across all four periods (2005, 2010, 2015, 2020), with the strongest impact in 2015 (coefficient = 0.643). Topographic factors such as elevation and slope also had positive effects, peaking at 0.304 in 2015. In contrast, human activities, especially GDP and nighttime light intensity, negatively impacted NPP, with the strongest negative effect in 2010 (coefficient = −0.567). These findings provide valuable scientific evidence for ecosystem management in Shandong Province and offer key insights for ecological restoration and sustainable development strategies at the national level.