The critical success factors that control hydrocarbon prospectivity in the Otway Basin have been investigated using petroleum systems approaches. It have revealed that greater than 99% of the discovered hydrocarbons in the Victorian Otway Basin have been sourced from Austral 2 (Albian-Aptian) source rocks and that these Austral 2-sourced hydrocarbon accumulations either directly overlie—or are located within 3,000 m—of actively generating Austral 2 source rock kitchens. Importantly, the zones of greatest prospectivity are located where these source rocks have been actively generating and expelling hydrocarbons throughout the Late Paleogene, primarily as a result of sediment loading associated with progradation of the Heytesbury shelfal carbonates. This peak generation window occurs at an average depth of approximately 2,500–3,500 m sub-mud across much of the basin, which has allowed prospective hydrocarbon fairways to be mapped out, thereby highlighting areas of greatest prospectivity. The close spatial proximity of the actively generating source rocks to the accumulations is due to several factors, which include overall poor fault seal in the basin (success cases occur where charge rate exceeds leakage rate) and relatively complex and tortuous migration fairways (which means that large volumes of hydrocarbons are only focussed and migrate for relatively short distances). In areas within which the Austral 2 system comprises the sole hydrocarbon charge—such as across the inner Mussel Platform—the reservoired gas compositions are typically very dry. In contrast, the gas compositions in accumulations sited along or immediately inboard of the Mussel-Tartwaup Fault Zone (La Bella, Geographe and Thylacine) are significantly wetter and also have higher CO2 contents. Throughout this area, the wetter components of the reservoired hydrocarbon inventory may have a source contribution from within the basal (Turonian) part of the younger Austral 3 system, in sequences that have been confirmed by δTLogR analysis to be significantly enriched in total organic carbon content. This observation has significantly upgraded the potential of the upper shelf areas, where a relatively more liquids-rich hydrocarbon inventory might be expected. The CO2 in accumulations located along the Mussel-Tartwaup Fault Zone is interpreted, based upon new helium isotope data, to be of mixed deep crustal-magmatic origin. This CO2 is believed to have migrated from great depth up the crustal-scale fault arrays into the shallower Late Cretaceous reservoirs. Here, the CO2 mixed with crustal gases, typified by helium with a mixed magmatic-crustal isotopic signature. Throughout this area, the traps tend to be large and hence—even though their CO2 contents are only 8–12%—the total CO2 volumes contained in these accumulations are much greater than those in the very CO2-rich—but volumetrically small traps—located onshore (e.g. Boggy Creek). Hydrocarbon accumulations located on the inner shelf, such as Minerva and Casino, have distinctly lower CO2 contents, perhaps because large displacement, through-going faults are lacking in this area. These observations collectively provide a predictive regional framework for understanding the likely distribution of commercial hydrocarbon accumulations in the offshore Otway Basin, as well as for forecasting the gas wetnesses and CO2 contents of undrilled exploration targets in both well-explored and frontier parts of the basin.