The social ecological model provides a comprehensive framework for understanding the multiple-level determinants of physical activity. This study explores the significant individual, social, and environmental variables and their interactions in relation to physical activity in middle-aged and older adults in Taiwan. A cross-sectional study design was implemented. Healthy middle-aged and older adults were recruited (n = 697) through face-to-face and online surveys. The data collected comprised self-efficacy, social support, neighbourhood environment, and demographic characteristics. Hierarchical regression was used for statistical analysis. Self-rated health (B= 74.74,p< .001;B= 101.45,p= .022) and self-efficacy (B= 17.93,p< .001;B= 14.95,p= .020) were the significant individual variables in both middle-aged and older adults. Neighbourhood environment (B= 6.90,p= .015) and the interaction between self-efficacy and neighbourhood environment (B= 1.56,p= .009) were significant in middle-aged adults. Self-efficacy was the most significant predictor for all participants, with the positive correlations of neighbourhood environment arising only for middle-aged adults with high self-efficacy. Policy making or project design should consider multilevel factors in order to facilitate their physical activity.