Background: Nowadays youth especially within secondary schools are exposed to different stressors in addition to academic stress causing psychological problems. Mental health and wellbeing have recently received public health attention especially among adolescents. Self- esteem and self-efficacy are main two components of the evaluative part of self-concept that contribute to mental well-being and psychosocial competence. This study aims to investigate whether self-esteem and self-efficacy serve as significant predictors of total difficulty score among Minia City secondary school students. Methods: A cross sectional design was conducted for the study with participation of 298 students in two randomly chosen secondary schools in Minia city during academic year 2021/ 2022. The measures used were standardized Strength and difficulties questionnaire for emotional problems (SDQ), Rosenberg self-esteem scale (RSES), General self-efficacy scale in addition to questions for student personal characteristics. Results: Students identified with low self-esteem constituted (27.5%) of total participants. Mean self-efficacy score was (28.75± 5.7). In univariate correlational analysis, Significant correlation was found between self- esteem, self-efficacy and total difficult score. In linear regression model, self-esteem, self- efficacy, gender, hours spent online, and perceived health issues strongly predicted emotional difficulties. Self-esteem was significant predictor for total difficulty in all models, with highest standardized coefficient B in model 3. Conclusion: Higher prevalence of low self-esteem (among more than quarter of students) compared to previous studies was found in this study. A confirmed finding is that low self-esteem was the most significant contributor. School intervention programs should be put in consideration to enable these students to learn how to face life challenges, teach them skills to maximize confidence and capacity building regarding their resilience.