ABSTRACT The Vaca Muerta Formation (Late Jurassic–Early Cretaceous) bears a high-quality, oil-prone kerogen deposited under mostly anoxic, marine conditions and constitutes a world-class source rock with outstanding geochemical characteristics for the generation of petroleum (oil and gas) throughout the Neuquén Basin. The formation has been identified as the main source for the majority of the hydrocarbon pools found in conventional reservoirs of the basin, but in the last ten years, it has also acquired significance as a self-sourced unconventional reservoir target for both oil and gas. An extended database that comprises several tens of thousands of samples, including cuttings, cores, sidewall cores, and outcrops of the Vaca Muerta Formation from wells and outcrop sections along the entire basin was evaluated. This allowed formulating patterns of organic richness, hydrocarbon source quality, and distribution of free hydrocarbons in six reference areas of the basin. These reference areas are defined based either on the impact of the sedimentary rock on generated hydrocarbons or on the significant thermal maturity differences. The areas are: Malargüe, Chihuido-Lomita, Northeast Platform, Embayment, Huincul Arch, and Picún Leufú. More than 300 oils and organic extracts from Vaca Muerta and nearly 500 mud and production gas samples completed the data set to understand the key features of the fluids occurring in the prospectable areas for unconventional resources (shale oil and shale gas). Collected and evaluated analytical data include total organic carbon (TOC), programmed pyrolysis, visual kerogen analyses, bulk chemical composition of fluids, gas chromatography (GC) and gas chromatography–mass spectrometry for biomarker fingerprints (GCMS), stable carbon isotopes, bulk and compositional kinetics, and x-ray fluorescence (XRF). Moreover, insights into the essential processes of the Vaca Muerta unconventional petroleum system including kerogen-related issues and basin-scale processes are discussed in terms of source rock kinetics, modeling of burial/exhumation histories, porosity development, and overpressure occurrence. The Embayment area stands out as the most attractive for unconventional development to produce middle-to-light oil with low sulfur content along with gas condensate westward. An analogous pattern is observed in the Chihuido-Lomita and Huincul Arch areas, with similar source rock characteristics but with overall lower thermal maturity compared with the Embayment area. However, in the transition to the Northeast Platform, the northeastern fringe of Chihuido-Lomita and Embayment areas present middle-to-heavy, mostly sulfur-rich oils, with limited gas potential, hence requiring higher permeability to yield commercial production. The Malargüe area is characterized by overall mid maturity and limited quality of oil (middle to heavy), predominantly sulfur-rich. Finally, the Picún Leufú area is conditioned by a source rock with low potential because of thinner organic-rich intervals and low-to-middle thermal maturity.