Robust constraints on Mesozoic-Cenozoic tectonic and topographic processes of the Pamir syntaxis is crucial to understanding the orogenesis and geodynamics of the Tibetan Plateau,as well as their impacts on the climate changes of Central Asia in the past. This review paper emphasized on the compilation of research progress on onset timing and evolution of major structures, burial and exhumation of the gneiss dome systems, as well as metamorphism and magmatism in the Pamirs and adjacent areas in recent decade, which are central to the topics of Mesozoic-Cenozoic morphtectonic evolution of the Pamir syntaxis, and Cenozoic incursions of the Tarim Sea. Episodic geodynamic scenarios were proposed to account for tectonic and topographic development of the Pamir-West Kunlun Mountains from the Permian to the Late Miocene. It is confirmed that the Pamir-West Kunlun Mountain belts are long-lived topographic expression dating back to Triassic-Early Jurassic times, and have experienced Middle-Late Mesozoic to Early Cenozoic rejuvenation and Late Oligocene-Miocene outward and upward expansion. The Eocene deformation of the Pamir-West Kunlun Mountains was minor compared with thickening of the crust initiated at ca. 37 ~ 35 Ma. Notably, large-scale northward indentation of the Pamirs did not occur until the Late Oligocene,responsible for the formation of orocline structures of the Pamir syntaxis. A model of double-sided lithospheric wedge model primarily driven by breakoff of the Indian crustal slab was built up to explain widespread intense tectonism in the Pamirs, featured by synchroneity of initial deformation of major structures, intense rock exhumation and burial peak metamorphism,associated with coeval magmatism across western Tibet. To the north the Pamir-West Kunlun Mountains, two steps of westward retreat of Paratethys Sea from the Tarim Basin took place at ca.41 ~ 40 Ma and ca. 39 ~ 37 Ma in time order. The timing of latest regression of Paratethys from the Tarim Basin partially overlapped with Eocene magmatism of the central Pamir and the onset of significant crustal thickening of central and southern Pamirs from ca. 37~35 Ma ago, implying potential impacts of regional tectonics on final sea retreat in the Tarim Basin. In addition, the oscillation of marine regression and transgression in Central Asia keeps pace with the drop-and-rise pattern of global sea level due to climate change, suggesting a role of climate change playing on the retreat of Tarim Sea in a long-term period. Therefore, both mechanisms of crustal thickening and descending of global sea level due to global cooling could control the final regression of the Tarim Sea. The relative contribution of tectonism and climate change to sea retreat from Central Asia still needs to be further evaluated.