Marine protected areas (MPAs) face many challenges in their aim to effectively conserve marine ecosystems. In this study we analyze the extent of pollution exposure on the global fleet of MPAs. This includes indicators for current and future pollution and the implications for regionally clustered groups of MPAs with similar biophysical characteristics. To cluster MPAs into characteristic signature groups, their bathymetry, baseline biodiversity, distance from shore, mean sea surface temperature and mean sea surface salinity were used. We assess the extent at which each signature group is facing exposure from multiple pollution types. MPA groups experience similar pollution exposure on a regional level. We highlight how the challenges that MPAs face can be addressed through governance at the appropriate scale and design considerations for integrated terrestrial and marine management approaches within regional level networks. Furthermore, we present diagnostic social-ecological indicators for addressing the challenges facing unsuccessful MPAs with practical applications.