Objectives: The study objective was to appraise the predictors affecting healthcare students’ perceptions concerning mental health challenges (MHCs) in a medical university. Methods: A cross-sectional observational study was conducted to associate the various predictors affecting the perception concerning the MHCs of health care students in a medical university in Malaysia. A self-prepared and validated questionnaire was distributed to the health care students in three different healthcare faculties (medical, pharmacy and dentistry) in a medical university. The required sample size for the current study was calculated using a convenient stratified sampling technique. The targeted minimum sample size was 250 participants from three different health care faculties. The Statistical Package for Social Science (SPSS) Version 24.0 was used to analyze and present the data. Results: From 284 study participants, female students had significantly better (p=0.003) perception than males. A statically significant association (p=0.032) was observed between faculty determinant and perception of pharmacy students. The final students had significantly better (p=0.018) perception as compared to pre-final year students. The students living in hostels had a better perception than non-hostellers. Parents’ education (p=0.029) and having health care professionals (p=0.002) in the family were directly associated with a better perception of health care students. Conclusion: Overall good perception of MHCs was observed among the studied cohort of the medical university’s health care students.