The Middle to Upper Eocene series are characterized by multiple hiatuses related to erosion, nondeposition, or condensed series in the Cap Bon and Gulf of Hammamet provinces. We have performed an integrated study taking advantage of surface and subsurface geology, faunal content, borehole logs, electrical well logs, vertical seismic profiles, and surface seismic sections. Calibrated seismic profiles together with borehole data analysis reveal unconformities with deep erosion, pinch outs, normal faulting, and basin inversion that are dated Campanian, intra-Lutetian, and Priabonian compressive phases; these events were also described at the regional scale in Tunisia. Tectonics, sea-level fluctuations, and climate changes closely controlled the depositional process during the Middle to Upper Eocene time. The depositional environment ranges from internal to outer platform separated by an inherited paleo high. We determine eight third-order sequences characterizing the interaction among tectonic pulsations, sea-level changes, and the developed accommodation space within the Middle to Upper Eocene interval. We correlate the obtained results of the Cap Bon-Gulf of Hammamet provinces with the published global charts of sea-level changes, and we find a good correspondence across third-order cycles. Model-based 3D inversion proved to be a solution to model the lateral and vertical lithologic distribution of the Middle to Upper Eocene series.