Sweet spots assessment within the Vaca Muerta formation in the Neuquén Basin of Argentina, is not only focused to the geological and geomechanical characterization of the rock but also to predict its production potential based on the composition of the existing fluid, its thermal maturity, and the pressures to which the prospective interval is subject. Compositional and isotopic analyses on gases extracted from the Vaca Muerta formation have shown geochemical anomalies, reflected as an enrichment in the proportion of light components of the gas and reversals in the normal trend of thermal maturity. The causal mechanisms involve complex physical-chemical processes, which include the in-situ cracking of oil and/or wet gas, with overpressure generation. It was determined that these anomalies occur in the middle and lower sections of the formation for wetness values below 5-7% and Ro values close to 1.76%. The overpressure is observed in the entire Vaca Muerta. Starts at the top, becoming higher, and more evident, at the bottom, in the lower enriched section. It coincides with the appearance- and increase- in beefs frequency and also in the proportion of coarse samples, expressed as cavings with angular, splinter, and tabular shapes of evident signs of overpressure and well instability. In parallel, an enrichment in the content of organic matter is observed. The study also reveals that there is a close relationship between fracture gradients and overpressures. When plotting the local fracture gradient of the wells, obtained from hydraulic stimulation, with the regional fracture gradient, and projected in depth, it is observed that the intersection matches with the start of a pressurized zone, the isotopic reversals, and with an increase in the dry gas. These results suggest the existence of several pressure compartments within Vaca Muerta, so its recognition and delimitation are fundamental for the impact on the design of wells, selection of zones to stimulate, and prediction of production potential, because of it analogy to very productive shales from other basins.