Marine Heat Wave (MHW) events are increasingly recognized as an important factor in the sustainability of coastal environments (both natural and urban), in the context of climate change. They are related to increasing trends of Sea Surface Temperature (SST) at the adjacent ocean waters. SST is an important parameter of the earth’s climate and increasing SST trends have been associated with adverse effects on coastal ecosystems, with important environmental and socioeconomic implications. This study focuses on the SST interannual variability over the coastal marine environment of South Florida, which contains several fragile ecosystems, and draws associate effects with adjacent large urban coastal settlements. The methodology is based on high-resolution satellite-derived SST data during a 40-year period (1982–2021), augmented by recent high-resolution model simulations (2012–2020). A generally increasing trend has been detected in the observations over the entire region (0.19 °C/decade). The unusual temperature levels have been associated with the formation of extensive MHW events, which showed interannual positive trends (0.75 events/decade) during the 40-year study period. Specifically, the six most recent years (2015–2021) were characterized by the strongest formation of MHWs with a peak in 2015, 2019 and 2020, with more than 8 events/year and approximately 70 to 110 days/year duration in total. The Florida Keys, especially along the Straits of Florida (southern island coasts), revealed very strong increasing trends. Miami Beach is also characterized by strong interannual trends (1.1 events/decade and 10 days/decade) compared to the enclosed basin of Biscayne Bay. In addition to the influence of atmospheric conditions over all regions around South Florida, the formation of MHWs near the eastern Florida coasts was also controlled by ocean dynamics, related to the warm Florida Current (FC). The evolution of the FC close to the eastern coasts (e.g., Miami Beach) was found to be a pre-condition of MHW formation. Several disastrous events on the biotic environment of South Florida near large urban settlements have been related to the formation of MHWs. The detected positive trends, and especially the recent high peaks of MHW events, may enhance the loss of specific heat-sensitive species, damaging the biodiversity of this tropical coastal environment and weakening the natural coastal protection against tropical storms. Urban planning for sustainable development in South Florida’s coastal cities must take into account MHW trends.