The eastern foothills in the Colombian Eastern Cordillera have been an important oil-producing region since the discovery of the Cupiagua and Cusiana fields. Three organic-rich units are considered to be the main source rocks. The Aptian Fómeque and the Cenomanian-Coniacian Chipaque Formations comprise a siliciclastic to locally carbonate shallow marine shelf succession with type-II kerogen, whereas the Paleocene Los Cuervos Formation consists of marginal marine to nonmarine siliciclastic rocks with type-III kerogen. We modeled the petroleum systems of these three source units to characterize the hydrocarbon generation-accumulation processes within the basin. The structural record of the Eastern Cordillera shows that the most important tectonic event began in early Oligocene with contractional deformation along the Soapaga through Guaicaramo faults during early Miocene, culminating during the Pliocene with the Cusiana and Yopal faults. These variable rates of burial and exhumation resulted in contrasting time-temperature histories for each of the source rocks. The Fómeque Formation reached the oil window during the Paleocene in the south and the Eocene to the north. In contrast, the Chipaque Formation generation started during Early Oligocene in the south and by Late Oligocene to the north. Conversely, maturation for the Los Cuervos Formation was uniform along the foothills, reaching the oil window during Late Oligocene. Charge history modeling suggested that the Albian sandstones reservoirs were filled between Oligocene to Miocene. In contrast, the proven reservoirs in the area (the Upper Cretaceous, Paleocene, and Eocene sandstones) were filled by late Miocene, with a second episode of recent charge in the Eocene reservoirs, and perhaps active, from the Los Cuervos Formation. The results of this work proved that petroleum system modeling is useful not only to characterize generation-migration processes but it also can be used as a prediction tool in structurally complex areas such as the Colombian foothills.