Conventional basin and petroleum systems modeling uses the vertical backstripping approach to describe the structural evolution of a basin. In structurally complex regions, this is not sufficient. If lateral rock movement and faulting are inputs, the basin and petroleum systems modeling should be performed using structurally restored models. This requires a specific methodology to simulate rock stress, pore pressure, and compaction, followed by the modeling of the thermal history and the petroleum systems. We demonstrate the strength of this approach in a case study from the Monagas fold and thrust belt (Eastern Venezuela Basin). The different petroleum systems have been evaluated through geologic time within a pressure and temperature framework. Particular emphasis has been given to investigating structural dependencies of the petroleum systems such as the relationship between thrusting and hydrocarbon generation, dynamic structure-related migration pathways, and the general impact of deformation. We also focus on seal integrity through geologic time by using two independent methods: forward rock stress simulation and fault activity analysis. We describe the uncertainty that is introduced by replacing backstripped paleogeometry with structural restoration, and discuss decompaction adequacy. We have built two end-member scenarios using structural restoration, one assuming hydrostatic decompaction, and one neglecting it. We have quantified the impact through geologic time of both scenarios by analyzing important parameters such as rock matrix mass balance, source rock burial depth, temperature, and transformation ratio.