We revisited the partitioning of the Mediterranean Sea into bioregions by processing satellite Sea Surface Temperature (SST) and Chlorophyll-a concentration (Chla) from ocean color observations combined with Argo mixed-layer depth for a period ranging from 2003 up to 2020. This regionalization was performed using an innovative classification based on self-organizing maps, the so-called 2S-SOM. We clustered the Mediterranean Sea waters into seven bioregions governed by specific physical and biogeochemical characteristics. We studied the interannual variability of these bioregions over the 18 years. We showed that the temperature is increasing with a mean rate of 0.4°C per decade. The chlorophyll-a concentration is quasi constant, but we evidenced a noticeable change in satellite-derived phytoplankton communities: Diatoms concentration is decreasing while cyanobacteria concentration is increasing. The bioregion trends could be related to global warming. The whole Mediterranean Sea is shifting to an eastern Mediterranean state.