The main focus of this study is the origin of the paleofluids in the Late Cretaceous–Oligocene sandstone reservoirs of the El Furrial structure (Venezuela). Basin modeling was performed using Thrustpack, Locace, and Ceres tools. The temperature and nature of the fluids obtained by this modeling were compared to fluid inclusions and oxygen isotope data on quartz overgrowth. Four stages should be considered in this area: (1) From 65 to 20 Ma: Fluids were at thermal equilibrium with the sediments. They were continuously expelled vertically toward the surface during compaction-driven dewatering processes. (2) From 20 to 12 Ma: As a result of the regional tilting and the deposition of the synflexural Naricual Formation, the Cretaceous and Oligocene sandstones of the El Furrial structure became efficient conduits for fluids circulating from the north. These fluids were at thermal equilibrium with the Cretaceous and Oligocene sandstones and seem to be correlated with the first generation of quartz overgrowths. This episode is characterized by an increase in the overpressure of the Oligocene and Upper Cretaceous sandstones that is correlated to a hydraulic fracturing of the sealing Carapita black shales. (3) From 12 to 8 Ma: Fluids were expelled laterally from the Cretaceous sediments of the Pirital hanging-wall unit that is located immediately north of the El Furrial structure. These fluids were likely in chemical disequilibrium, and their temperature was higher than the temperature of adjacent sediments, which probably resulted in additional but minor episodes of quartz precipitation. This hypothesis is consistent with the information obtained from oxygen isotope analyses, which suggest that subsequent generations of quartz cement probably formed from evolved basinal fluids. (4) A reduction of the intensity of the flow and then an inversion of this flow mark the sealing of the southern structural closure of the structure at about 8 Ma. Then, the closure of the northern flank occured at about 5 Ma, as indicated by a present velocity of the fluids close to zero in the El Furrial reservoirs and the filling of the structure by the hydrocarbons.