The rapid development of social media has influenced the psychological dynamics of students, particularly related to Fear of Missing Out (FoMO) and the formation of self-esteem. Instagram is one of the most widely used platforms among students and facilitates social comparison that may influence individual self-evaluation. This study aims to analyze the influence of FoMO and Instagram usage on the self-esteem of students at Islamic religious universities. This research employed a quantitative approach with a correlational design. The participants consisted of 82 students from the State Islamic University of Palangka Raya who were selected through purposive sampling with the criterion of actively using Instagram. Data were collected using a questionnaire with a Likert scale measuring FoMO, Instagram usage, and self-esteem. Instrument validity was tested using Pearson Product Moment correlation, while reliability was examined using Cronbach’s Alpha coefficient. The data were analyzed using multiple linear regression analysis. The results showed that the regression model was significant (F = 11.657; p < 0.05) with a coefficient of determination (R² = 0.229), indicating that 22.9% of the variance in self-esteem could be explained by FoMO and Instagram usage. Partial testing showed that FoMO had a negative and significant effect on self-esteem (t = -3.173; p = 0.002), whereas Instagram usage did not significantly affect self-esteem (t = -1.258; p = 0.211). These findings indicate that digital social anxiety such as FoMO plays an important role in shaping students’ self-esteem in the social media era.