This study investigated the association between internalized stigma and hope, self-esteem, self-efficacy, and treatment adherence and explored the most influential and predictive factor of internalized stigma among patients with severe mental disorders. This correlational descriptive study was conducted on 257 outpatients diagnosed with severe mental illness according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) diagnostic criteria. The participants were seeking treatment at outpatient and affiliated clinics of Razi Hospital, Iran, from October 2018 to May 2019. We used a convenient sampling design. Internalized Stigma of Mental Illness scale, Dispositional Hope Scale, Rosenberg's Self-Esteem Scale, General Self-Efficacy Scale, and Drug Attitude Inventory were used to gather data. The data were analyzed using inferential statistics (Pearson correlation, coefficient logistic, and regression analyses) at a 0.05 significance level. The mean (standard deviation) score of internalized stigma was 1.57 (0.49), and 58% of the participants reported moderate to high internalized stigma. A negative significant relationship was found between internalized stigma and hope (r = -0.55, p < 0.05), self-esteem (r = -0.66, p < 0.05), and self-efficacy (r = -0.64, p < 0.05). Treatment adherence was not found to be significantly associated with the internalized stigma. In the final regression model, self-esteem and self-efficacy significantly predicted internalized stigma. Given the crucial role of self-esteem and self-efficacy in predicting internalized stigma, nurses should devote special attention to these factors and use strategies to improve individuals' self-esteem and self-efficacy.