ABSTRACT The Madre de Dios Basin, located in the northern sub-Andean zone of Bolivia is an underexplored sub-Andean basin. A complete stratigraphic revision, including biostratigraphy, core description, and sismo-stratigraphy, has been carried out; it suggests some changes in the historical sedimentary models and allows the identification of several reservoir and seal pairs. This revision not only integrates the results of previous studies but also provides new and original interpretations of the existing data set. The geochemical study indicates the existence of an Upper Devonian world-class source rock, in which, the Frasnian interval is characterized with a type I-II kerogen and a source potential index (SPI) higher than 6 ton/m 2 ; the Famennian interval has a type II kerogen and its SPI reaches 3 t/m 2 . The Carboniferous and Permian formations have levels with notable content of organic matter but do not classify as source rock in this area because of their low SPI. To evaluate the hydrocarbon potential of the basin, a 3-D dynamic model has been built. The thermal calibration of the temperature and maturity data is only possible taking into account an increase of the heat flow during Triassic–Jurassic time. As a consequence, 90% of the hydrocarbons are expelled before Cretaceous times by the identified kitchen in the center of the basin. The remaining 10% were expelled between the Oligocene and present time. Considering a petroleum system yield of 1%, the yet to find (mean) of the studied area is evaluated at 7 Gbbl of oil equivalent. The main challenge of the basin remains in finding traps.