The ongoing mpox outbreak in sub-Saharan Africa has highlighted the critical need for equitable vaccine access and robust logistical support. However, these factors alone are insufficient to ensure the success of vaccination campaigns in regions characterized by unique epidemiological and immunological challenges. One significant issue is the high prevalence of helminth infections, which are known to impair immune responses to vaccines, potentially reducing both short-term efficacy and long-term antibody titers. This paper explores the implications of helminthiasis for mpox vaccination in sub-Saharan Africa, emphasizing the need for integrated strategies to address this co-infection. We discuss whether combining deworming programs with vaccination campaigns could enhance vaccine responses and examine the applicability of emerging data on single-dose mpox vaccination in the context of endemic helminth infections. Furthermore, we highlight the importance of real-time surveillance to monitor vaccine effectiveness and identify breakthrough infections in regions with high helminth prevalence. Our findings underscore the necessity of a context-specific approach to mpox vaccination policies, one that considers the intricate interplay between helminth infections and vaccine efficacy. Addressing these challenges is essential to ensure the success of vaccination efforts and to mitigate the broader public health impact of mpox in Africa and beyond.