The vegetation carbon sink in the Indochina Peninsula plays an important role in the global ecosystem carbon cycle, but research on changes in the vegetation carbon sink in this region is quite limited, especially in karst ecologically fragile areas. Utilizing the improved CASA model and soil respiration empirical equation, combined with a variety of remote sensing data, this study estimated the net ecosystem productivity (NEP) of vegetation in the karst mountainous areas of the Indochina Peninsula. Trend analysis, partial correlation analysis and geographical detectors were also adopted to explore its spatial-temporal changes and driving factors. The results showed that: (1) From the perspective of spatio-temporal changes in vegetation NEP, the annual average vegetation NEP in the study area experienced a decline between 2000 and 2020, with a declining rate of 2.66 gC m-2a-1. The karst area experienced the fastest declining rate, particularly in Laos, Vietnam, and Cambodia, where it reached 4.11 gC m-2a-1. The total carbon sequestration of vegetation in the carbon sink area decreased rapidly, reaching 5.17 TgC/a. (2) From the perspective of driving factors in vegetation NEP, the joint effect of temperature, precipitation, and solar radiation constituted the main climate driving factors affecting vegetation NEP. Secondly, the vast majority of land-use changes resulted in a decrease in total vegetation carbon sequestration. Additionally, greater reductions in vegetation carbon sequestration were observed in areas where forested land and cropland remained unchanged. Lastly, vegetation cover changes and altitude distribution were the primary natural driving factors affecting the spatial differentiation of vegetation NEP, while land use changes, population distribution, and land reclamation constituted the primary anthropogenic driving factors. The interactions between factors were enhanced. The research results can contribute to our understanding of the vegetation carbon cycle status in the area and provide valuable suggestions for restoration.