Abstract To address the underreporting of mpox cases in endemic regions, a regional surveillance network, known as the Mpox Threat Reduction Network (MPX-TRN), was established between five neighboring countries in Central and West Africa in 2022. One direct outcome of the MPX-TRN has been the strengthening of regional mpox surveillance. This consortium has facilited open communication channels, detection of cross-border mpox cases, and improvements of the detection and diagnosis of mpox in Central Africa and worldwide. Importantly, the MPX-TRN provides a scalable model for addressing underreporting of diseases, such as mpox.