<p>The World Health Organization (WHO) has declared public health emergency of international concern (PHEIC) for the multinational outbreak of mpox in 2024, due to clade I Monkeypox virus (MPXV). Our team conducted a questionnaire-based cross-sectional study to investigate the knowledge and attitudes of 902 health science students (who were studying dentistry, physiotherapy, pharmacy, or nursing) in India and Bangladesh. The mean knowledge and attitude scores were 14.4 ± 3.6 and 7.7 ± 1.9, respectively. Despite high (&gt; 85%) awareness of Mpox outbreaks and cognizance of the declaration of PHEIC, noteworthy misconceptions were also noticed: 55.9% thought that MPXV infection could be treated with antibiotics, and there was an increased case fatality estimation. Approximately 91% of students preferred post-infection isolation and relied on vaccination. Nearly three-fourths of them were concerned about the pandemic potential of MPXV. Based on the multivariable models, we found that students ≥ 26 years of age (β = 2.23; 95% CI 0.97–3.50) and those with prior information-seeking behavior through Google, ChatGPT, etc. (β = 1.46; 0.97–1.96) independently predicted higher knowledge. These patterns were also observed for attitudes (β = 0.84, 0.23–1.45). Interns/residents showed better scores, while third-year students displayed lower knowledge (β = −1.42; −2.75 to − 0.09). These findings show that there is scope for readiness, but there are gaps in therapeutic and risk management. This study underscores the need for incremental activities to augment digital and curricular literacy for combating public health emergencies in low-resource academic milieu.</p>