This study aims to fill in a gap by examining how physical activities (PAs), feeling good about oneself physically, and academic performance (ACD_PRF) all work together to influence the overall quality of life (QoL) for vulnerable students. We examined data from 400 vulnerable students studying in various universities and major specializations. We employed the Partial Least Squares–Structural Equation Modeling (PLS-SEM) data-analysis technique to test the validity and reliability of the outer model and to test the hypotheses used in the inner model. The research findings indicate that physical activities and physical self-esteem (PHS) can directly and indirectly improve vulnerable students’ QoL. However, among vulnerable students, ACD_PRF can only strengthen their QoL indirectly through improving their PHS. These findings help us to understand how physical activities, feeling good about one’s body, and ACD_PRF all contribute to these students having a better overall QoL. This knowledge can help us to develop better ways to support vulnerable students and to improve their well-being in all aspects of their lives, bodies, and ACD_PRF, which contributes to these students having a better overall QoL. This knowledge can help us to develop better ways to support students with disabilities (SwDs) and to improve their well-being in all aspects of their lives.