Admission to engineering and medical colleges in India is determined through entrance exams, like the Joint Entrance Exam (JEE) and the National Eligibility Entrance Test (NEET), with millions of candidates facing rigorous competition. Declining mental health among these students is well documented; however, research on non-suicidal self-injury (NSSI) remains limited. The hypothesized model is based on the Integrated Theoretical Model of NSSI and Meaning in Life theory, which conceptualize NSSI as emerging from the combination of emotional vulnerability and stress, with mattering as a protective factor, respectively. A moderated-mediation model was examined. The current study aimed at testing a hypothesized moderated-mediation model to check the relationship of academic stress, perceived parental expectations, and mattering with NSSI among NEET and JEE aspirants. A total of 151 NEET and JEE aspirants (M = 18.45; SD = 1.97) participated in the study. A survey based on standardized questionnaires was used as a data collection tool. The reported prevalence rate of NSSI was 45.69%, which is higher than global prevalence but consistent with prior prevalence rates in Indian and South Asian samples. The study found that PPE and NSSI were indirectly associated through academic stress (β = 0.128, b = 0.044, SE = 0.015, p = 0.003, 95% CI = [0.020, 0.081]), and mattering moderated the relationship between PPE and academic stress (β = −0.159, b = −0.063, SE = 0.026, p = 0.015, 95% CI [−0.115, −0.004]). The findings suggest that mattering serves as a protective factor from NSSI in high-stakes academic environments and provides further implications for culturally informed NSSI prevention among these individuals. This further represents a novel contribution to the literature by clarifying its buffering role against NSSI among NEET and JEE aspirants.