EIGEN 6C4 gravity anomalies are interpreted to determine the lateral and vertical variations in the crust and upper mantle structure and their influence on the isostasy of the coastal plain, transition zone between the Congo Craton (CC), the Pan-African Belt (PAB), and adjacent areas. The regional gravity anomalies have been inverted in an attempt to provide a Moho depth map. The inversion process was based on the Parker-Oldenburg method with a density contrast of 0.55 g/cm3 and an average depth reference of 39 km. In addition, various tests have been performed to validate the resulting Moho model and estimate the efficiency of the 3D gravity inversion by varying the density contrast for a fixed Moho reference depth. Inversion results reveal that the Moho depths generally agree with those obtained from previous geophysical studies. The computation of the isostatic models using the ETOPO1 digital elevation model (DEM) and its comparison with the Moho models obtained from gravity induce the following main conclusions: (1) an overcompensated crust beneath the coastal plain and the Yaounde Domain, (2) the crust beneath areas located in the southern end of the Adamawa-Yade Domain is thin and undercompensated, and (3) main volcanoes of the Southwestern Cameroon Volcanic Line (CVL) are isostatically undercompensated. This study also revealed that the local isostatic compensation law is not satisfied for most of the tectonic provinces of the study area, and we suggest alternative tectonic mechanisms to support topography below these tectonic features. Additionally, most seismic events (M>3.5) occurred in areas marked by abrupt changes in compensation amplitude. Thus, we concluded from this study that the northern limit of the CC, the Mount Cameroon, and its surroundings are tectonic extension areas that may play a crucial role in the occurrence of future earthquakes.