Microphytobenthos (MPB) at the sediment surface of intertidal mudflats are known to show a high spatial and temporal variability in response to the biotic and abiotic conditions prevailing at the mud surface. It makes long-term and large-scale monitoring of MPB Gross Primary Production (GPP) difficult to set up. In this study, we developed the first 3D physical-biological coupled model (MARS-3D) that explicitly simulates GPP of intertidal MPB at the mudflat scale, and we compared the outputs with in situ and space remote sensing MPB GPP data. We discuss the sources of discrepancies between the modeling and the remote sensing approach in the light of future developments to be done. For instance, the remote sensing algorithm provides a very synoptic view of the mudflat GPP. It is well-suited to achieve diagnostic estimates of MPB GPP at the synoptic spatial and temporal scale. By contrast, the MARS-3D model provides a more dynamic representation of the MPB activity and prognostic estimates of MPB GPP over the mudflat. It is very relevant to resolve the seasonal and inter-annual dynamics of MPB. Getting comparable GPP estimates derived from the remote sensing algorithm and 3D physical-biological coupled model will further require a better convergence in terms of equations structure, biological constants parameterization, and source data used (i.e., vegetation index vs. chlorophyll a). Setting a common parameterization in both the numerical model and remote sensing algorithm might be challenging in a perspective of mapping MPB PP over large mudflats from a synoptic to inter-annual time scale, but it could open the door to a new way of quantifying MPB GPP over large intertidal mudflats.