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The ongoing global epidemic of mpox shows characteristics of sexually transmitted infections (STIs), with men who have sex with men being particularly vulnerable to infection. While the Republic of Korea has only reported around fifty confirmed mpox cases, preparing for a potential epidemic is imperative. To investigate private areas such as sexual contact, appropriate interview skills should be utilized while protecting the rights of vulnerable populations. Previous epidemiologic investigations and global principles employed while investigating HIV and STIs suggest involving vulnerable populations in the investigation. It is essential to establish investigation principles and mpox policies that consider the unique features of vulnerable populations to prevent stigma and discrimination against them. Moreover, such policies promote their engagement in the fight against the disease.