The analysis of synoptic satellite data of total chlorophyll-a (Chl-a) and the environmental drivers that influence nutrient and light availability for phytoplankton growth allows us to understand the spatio-temporal variability of phytoplankton biomass. In the Panama Bight Tropical region (PB; 1–9°N, 79–84°W), the spatial distribution of Chl-a is mostly related to the seasonal wind patterns and the intensity of localized upwelling centers. However, the association between the Chl-a and different physical variables and nutrient availability is still not fully assessed. In this study, we evaluate the relationship between the Chl-a and multiple physical (wind, Ekman pumping, geostrophic circulation, mixed layer depth, sea level anomalies, river discharges, sea surface temperature, and photosynthetically available radiation) and chemical (nutrients) drivers in order to explain the spatio-temporal Chl-a variability in the PB. We used satellite data of Chl-a and physical variables, and a re-analysis of a biogeochemical product for nutrients (2002–2016). Our results show that at the regional scale, the Chl-a varies seasonally in response to the wind forcing and sea surface temperature. However, in the coastal areas (mainly Gulf of Panama and off central-southern Colombia), the maximum non-seasonal Chl-a values are found in association with the availability of nutrients by river discharges, localized upwelling centers and the geostrophic circulation field. From this study, we infer that the interplay among these physical-chemical drivers is crucial for supporting the phytoplankton growth and the high biodiversity of the PB region.