This study investigates the influence of students’ knowledge on English for Specific Purposes (ESP) learning outcomes among Vietnamese economics university students. Drawing on data originally collected for a doctoral dissertation, the article focuses on the composite construct of students’ knowledge, which integrates specialized vocabulary (TVCN), disciplinary knowledge (KTCN), and communicative English (TAGT). Reliability analysis confirmed strong internal consistency for all four scales (Cronbach’s alpha ranging from 0.833 to 0.929). Exploratory factor analysis demonstrated that the nine indicators of students’ knowledge loaded onto a single latent factor, explaining 57.3% of the total variance. PLS-SEM further established construct reliability (CR > 0.87) and convergent validity (AVE > 0.60). Structural equation modeling revealed a significant positive relationship between students’ knowledge and ESP learning outcomes (β = 0.30, p < 0.001), with students’ knowledge accounting for 15% of the variance in the outcomes (R² = 0.15). These findings highlight the pivotal role of specialized vocabulary, disciplinary content knowledge, and communicative English competence in shaping ESP achievement. The study contributes to ESP pedagogy and applied linguistics by underscoring the necessity of integrated knowledge development rather than isolated skill training. Practical implications for curriculum design and teaching practice are also discussed.