Background <p>Although previous research has explored socioeconomic factors associated with syphilis, most studies have been limited to provincial or city-level analyses or have focused primarily on hotspot detection, with limited attention to the spatiotemporal heterogeneity of these associations. This study integrated data from 31 mainland Chinese provinces from 2006 to 2022 and applied geographically weighted principal component analysis (GWPCA) and geographically and temporally weighted regression (GTWR) to examine the ecological associations between socioeconomic and healthcare-related factors and reported syphilis incidence across space and time. These analyses provide empirical evidence to support spatially differentiated public health strategies.</p> Method <p>This study used annual reported syphilis incidence rates from 31 mainland Chinese provinces between 2006 and 2022 to describe spatial and temporal patterns using incidence maps and global Moran’s I. Kernel density estimation was used to examine temporal changes in the distribution of provincial incidence rates. Twelve provincial-level indicators were grouped into four domains: economic development, healthcare capacity, transportation infrastructure, and educational attainment. After standardization, GWPCA was applied to derive four localized composite scores, which were then used as predictors in a GTWR model to assess their spatiotemporally varying ecological associations with reported syphilis incidence.</p> Results <p>From 2006 to 2022, China’s reported syphilis incidence increased overall from 12.80 per 100,000 population in 2006 to a peak of 38.37 per 100,000 in 2019, followed by a decline to 31.27 per 100,000 in 2022. Higher reported incidence rates were observed in several eastern coastal and western provinces. Spatial autocorrelation analysis revealed a U-shaped trajectory in Moran’s I values, reaching statistical significance in all years except 2011–2013 and peaking in 2022 (Moran’s I = 0.479, <i>P</i> &lt; 0.05). Kernel density estimation indicated a rightward shift and widening of the provincial incidence distribution, suggesting increasing interprovincial disparity, although the distribution remained largely unimodal without clear evidence of polarization. GTWR revealed spatially and temporally heterogeneous associations. Economic development was generally negatively associated with reported syphilis incidence, whereas healthcare capacity showed a generally positive association, possibly reflecting enhanced case detection, screening access, and reporting completeness in better-resourced regions. Transportation infrastructure was positively associated with reported incidence, while educational attainment was generally negatively associated, especially in the northwestern region.</p> Conclusion <p>This study identified marked spatiotemporal heterogeneity in reported syphilis incidence across China from 2006 to 2022. The ecological associations between provincial socioeconomic and healthcare-related factors and reported incidence varied across regions and years. Economic development and educational attainment were generally negatively associated with reported incidence, whereas healthcare capacity and transportation infrastructure showed generally positive associations. These positive associations may partly reflect improved detection, screening, reporting, healthcare access, and population mobility rather than direct causal effects on transmission. The findings support spatially targeted public health strategies in high-burden regions, while emphasizing that the observed associations should not be interpreted as evidence of causality.</p>