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Continental collision is a crucial process in plate tectonics, whereas our understanding regarding the tectonic complexities at such convergent plate boundary remains largely unclear in terms of the evolution and the controlling parameters of its lateral heterogeneity. In this study, we conducted a series of two-dimensional numerical experiments to investigate how continental lithospheric thermal structure influences the development of lateral heterogeneity along the continental collision zone. Two end members were achieved: 1) Continuous subduction mode, which prevails when the model has a cold procontinental moho (Tmoho ≤ 450 °C). In this case, a narrow collision orogen develops, and the subducting angle steepens with the increasing retrocontinental Tmoho. 2) Continental subduction with a slab break-off, which generates a relative wide collision orogen, and dominates when the model has a relative hot procontinental Tmoho (≥ 500°C), especially when the Tmoho ≥ 550 °C. In contrast, Hr is the second-order controlling parameter in varying the continental collision mode, while it prefers to enhance strain localization in the upper part of the continental lithosphere and promote the growth of shear zones there. By comparing the model results with geoscience observations, we suggest that the discrepant evolutionary paths from the continuous subduction underlying the Hindu Kush to the continental subduction after slab break-off beneath eastern Tibet may originate from the inherited lateral inhomogeneity of Indian lithospheric thermal structure. Besides, the high content of crustal radioactive elements may be one of the important factors that controls the formation of large thrust fault zones in the Himalayas. [ABSTRACT FROM AUTHOR]