On August 14, 2024, following a regional declaration by the Africa Centres for Disease Control and Prevention, the World Health Organization declared mpox a Public Health Emergency of International Concern, marking the second such declaration in two years. A series of outbreaks involving the more virulent clade I virus (compared to clade II, which caused a global outbreak in 2022), has now spread in 13 African countries, exposing the inadequacies of the public health infrastructure in these settings. There was significant investment during the 2022 global outbreak, but these efforts failed to address vaccine access and treatment in the Global South. Regulatory delays, unequal access to vaccines, and a lack of compassionate use treatments for severe cases have resulted in preventable cases and deaths, especially among vulnerable populations such as pregnant women, children, and the immunocompromised. The current outbreak also underscores critical knowledge gaps in our understanding of mpox, including its transmission, pathogenesis, and viral evolution. We join intensified calls for global solidarity and action to control mpox, emphasizing immediate containment measures and long-term local and international investment in African public health systems, to prevent future epidemics.