The hydrocarbon accumulation modes and differences in the Tethyan realm serve as a hot research topic in the petroleum geology community at home and abroad. Both the Persian Gulf Basin in the Middle East and the Sichuan Basin in China, situated on the southern and northern sides of the Tethyan realm, respectively, record the whole geological process of the opening and closure of the Prototethys, the Paleotethys, and the Neotethys sequentially, exhibiting anomalous hydrocarbon enrichment Based on the analysis of the plate tectonic evolution in the Tethyan realm, this study dissects the structures and hydrocarbon accumulation conditions of both basins. Followed by a systematic comparative analysis of the factors controlling hydrocarbon enrichment in the process of plate breakup and convergence in the Tethyan realm, this study proposes petroleum exploration targets in the realm. The results are as follows: (1) Since the Meso-Neoproterozoic, the Persian Gulf Basin and the Sichuan Basin have undergone similar tectonic evolution in the early stage but different in the late stage. Under the influence of the formation and evolution of the Prototethys, Paleotethys, and Neotethys oceans, both basins experienced multi-stage development and modification, forming two major extension-convergence cycles. Consequently, both basins are characterized by the vertical orderly superimposition of various basin prototypes in the order of rift-intracratonic basin (passive continental margin)-foreland. (2) The fact that the Tethyan realm was long located at medium-low latitudes and the local anoxic environment formed in the process of plate breakup and convergence played a vital role in the formation of extensive source rocks. The source rocks are predominantly distributed in underfilled rifts and deep depressions that were connected to the ocean in the unidirectional continental breakup process; basin-slopes and intra-shelf basins on passive continental margins; basinal lows within intracratonic basins, and underfilled foredeeps in foreland basins. The favorable areas for the formation of carbonate reservoirs include platform margins, submarine highs and paleo-uplifts within platforms, and fault zones. The evaporite cap rocks, intimately associated with the basin evolutionary stages and global dry-hot events, are critical for large-scale hydrocarbon preservation. (3) Under the influence of Tethyan evolution, the Persian Gulf Basin and the Sichuan Basin share similar primary factors controlling hydrocarbon enrichment. The moderate tectono-sedimentary differentiation and structural modification in the process of prototype basin superimposition, as well as the spatio-temporal matching of elements critical for hydrocarbon accumulation, are beneficial for the development of large oil and gas fields. The macroscopic hydrocarbon distribution is dictated by source rock-cap rock assemblages, while the local hydrocarbon distribution is governed by trap-reservoir assemblages. The critical factors determining the differential hydrocarbon enrichment in the Persian Gulf Basin and the Sichuan Basin include plate size and position, basement stability, eustatic movement, paleoclimate, and tectonic transformation. Besides, different tectonic modification intensities are closely related to the type, enrichment degree, and distribution of hydrocarbon reservoirs.