In low-lying estuarine regions, compound flooding (CF) is caused by the co-occurrence of extreme precipitation, river flooding and storm surge. In recent decades, there has been a rise in the frequency and intensity of pluvial-coastal CF events in different parts of the U.S. due to the increased frequency of intense precipitation and storm surge events. However, in estuarine and deltaic regions, the CF characteristics depend mainly on the storm tide and river flow interaction. Understanding how the fluvial-coastal CF may respond to changes to watershed and estuarine characteristics is essential for future CF hazard prediction. This study examined two critical processes: (a) the interplay between antecedent soil moisture conditions and peak river flow, and (b) how the impact of sea level rise (SLR) on storm surge and river flood distribution alters the CF in complex estuaries. As the study area, we selected the Delaware Bay and River, a shallow and convergent estuary in the US Mid-Atlantic region—where flood hazards during a CF can become more significant than the surge and river flood processes occurring in isolation. For the focal event for the study, we selected Hurricane Irene (2011) because it reportedly produced the most extreme CF over the past two decades in the same region. Ultimately, our results illustrated that the potential changes to the catchment and bay characteristics from the global temperature increase and SLR could significantly modulate the fluvial-coastal CF variability. The potential increase in global temperature and rainfall intensity might not always exacerbate the CF.