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Objectives: The objective of the study was to evaluate the determinants affecting knowledge of healthcare students towards mental health challenges (MHCs) in a private medical university. Methods: A cross-sectional observational study was conducted to correlates the different determinants of university students with their knowledge towards MHCs in a private university in Malaysia. Validated questionnaires were distributed using a convenient stratified sampling technique among students studying in the different healthcare faculties, namely medicine, pharmacy and dentistry. The Statistical Package for Social Science (SPSS) Version 24.0 was used to analyze the data. Results: Among 284 study participants, male students had less adequate knowledge than females. The majority of the students from the studied faculties had adequate knowledge of MHCs. Students of the age group of 25-30 years had adequate knowledge of MHCs. Multiple logistic regression revealed that statistically significant differences (p<0.05) were present among the three studied variables i.e., faculty, year of education and healthcare professionals in the family. Conclusion: Overall good knowledge of MHCs was observed among the studied cohort of the healthcare students of the private medical university. The present study concluded that faculty, year of education and healthcare professionals in the family were the observed determinants of knowledge about MHCs among the study participants. [ABSTRACT FROM AUTHOR]