A full grasp of the epidemiological factors promoting transmission is necessary for responding to highly infectious diseases, which involves their control and prevention. With the recent outbreak of Marburg Virus Disease (MVD) in Equatorial Guinea, we saw the need to re-shed some technical light based on our field experiences and published literature. We reviewed 15 previous MVD outbreaks globally. Coupled with core One-Health approaches, we highlighted the SPIN (socio-environmental context, possible transmission routes, informing and guiding public health action, needs in terms of control measures) framework as a guiding tool for response teams to appropriately approach this highly contagious infectious disease outbreak for collective and stronger global health security. The Central African Regional Collaborating Centre (RCC) of the Africa Centres for Disease Control and Prevention (Africa CDC) has a big lead role to play, most especially in coordinating the community engagement and risk communication packages of the response, which is highly needed at this point. We reiterate that this framework remains relevant, if not timely, in rethinking pandemic preparedness and response in resource-limited settings.