High-speed rail (HSR) station areas play a vital role in shaping urban form, stimulating economic activity, and enhancing spatial vitality. Understanding the factors that influence this vitality is key to supporting sustainable urban development and transit-oriented planning. This study investigates 66 HSR station areas in 35 Chinese cities by integrating multi-source data—Sina Weibo check-in records, urban support indicators, station attributes, and built environment variables—within a city–node–place analytical framework. Using Multiple Linear Regression (MLR) and Light Gradient Boosting Machine (LightGBM) models, we identify key drivers of spatial vitality, while SHAP analysis reveals nonlinear and interaction effects. The results show that city population size, urbanization level, commercial land use, transit accessibility, and parking facilities significantly enhance station area vitality. However, diminishing returns are observed when commercial land and bus stop densities exceed certain thresholds. The station location index shows a negative correlation with spatial vitality. The analysis of interaction effects highlights strong synergies between urban development and functional configuration, as well as between accessibility and service infrastructure. Different station types exhibit varied spatial patterns and require differentiated strategies. This study offers empirical insights for aligning transport infrastructure and land use planning, supporting the development of vibrant, accessible, and sustainable HSR station areas.