<p>Virtual scientific inquiry (VSI) environments are critical information technologies for improving the quality of education. However, the issue of students’ cognitive-affective profiles has received little attention, making it difficult to promote both cognitive achievements and positive affective factors. Based on the log-files and self-report data from 569 students, our study proposes a solution that integrates both theoretical underpinnings (including Cognitive Constructivism, Self-efficacy Theory, Flow Theory, Gender Schema Theory, and Control of Variable Strategy) and AI algorithms-driven analyses (i.e., unsupervised machine learning, pattern mining, and statistical analyses) to address this issue. Specifically, our study identifies two profiles: 350 thriving students and 219 struggling students, through the analysis of inquiry achievements, self-efficacy, and flow experience. Moreover, we found no significant gender difference between the two cognitive-affective profiles. Finally, we found that while thriving and struggling students shared similar foundational characteristics, thriving students exhibited more strategic behavioral frequencies and patterns. These findings can advance understanding of theoretical underpinnings and guide targeted support for students in VSI.</p>