This study examines the impact of e-commerce on the economic growth of small and medium-sized enterprises (SMEs) in Ho Chi Minh City, Vietnam. Grounded in the Technology-Organization-Environment (TOE) framework and Resource-Based View (RBV) theory, the research investigates five key factors: IT infrastructure, e-commerce capability, digital marketing, business data analytics, and employee IT skills. Using a quantitative approach, data were collected from 222 SMEs operating in e-commerce through structured questionnaires with a 5-point Likert scale during August-October 2025. The data were analyzed using SPSS 26.0, employing Cronbach's Alpha reliability testing, exploratory factor analysis (EFA), Pearson correlation analysis, and multiple linear regression. Results demonstrate that all five factors positively and significantly influence SME economic growth, with the model explaining 67.2% of the variance (R² = 0.672, F = 88.446, p < 0.001). IT infrastructure emerged as the strongest predictor (β = 0.301), followed by digital marketing (β = 0.277), e-commerce capability (β = 0.249), business data analytics (β = 0.242), and employee IT skills (β = 0.117). All hypotheses were supported with high statistical significance. The findings provide valuable insights for SME managers to prioritize investments in digital infrastructure and marketing strategies, while policymakers should develop supportive policies for digital transformation. This research contributes to the literature by providing empirical evidence of specific e-commerce factors driving economic growth in SMEs within an emerging market context.