The ongoing epidemic outbreak of mpox virus infection in Africa raises worldwide health concerns due to its potential for rapid international spread. The immediate risk of mpox to Southeast Asian nations, which are geographically distant from the region, is currently low. However, the global experience of COVID-19 has demonstrated that proactive measures are essential to prepare for any potential cases that may arise from travel or trade. A vaccine and antivirals against the mpox virus do exist, yet supply of both is very limited and their access is inequitable. In all but high-income countries, confirmatory molecular diagnostic testing is also not performed routinely by most microbiology diagnostic services, especially those in the mainstream public sector. Therefore, detection, infection control, and prevention rely heavily on community surveillance of suspected cases based on clinical presentation. The potential threat posed to Vietnam, a lower-middle income country in Southeast Asia, illustrates the current inadequacy of epidemiological surveillance and pathogen control. The World Health Organization declaration of mpox as a “public health emergency of international concern” is a global wake-up call to action. The escalation of a virulent and contagious infectious disease in another continent should be very closely monitored by each nation’s public health authorities. Moreover, capacity to rapidly instigate preventive measures relating to transmission routes, exposure settings, and vulnerable populations should be improved.