Abstract: As a promising new generation of biocompatible nanocarriers, microvesicles have garnered significant attention in targeted drug delivery owing to their unique capabilities in transmembrane transport and dynamic topological reorganization. However, existing theories of microparticle transport are mostly built on the rigid particle assumption, which fails to capture the bidirectional fluid-membrane coupling behavior of flexible microvesicles at the cellular scale. This limitation has resulted in a lack of systematic understanding regarding their transport mechanisms within complex microvascular networks. To bridge this knowledge gap, the present study employs the mesoscale simulation framework of dissipative particle dynamics (DPD) to develop two structurally and mechanically distinct microvesicle models: a microvesicle with fluidic membrane model (Mv-FMM; emulating liposome-based carriers with high membrane fluidity) and a microvesicle with viscoelastic network model (Mv-VNM; representing polymer-modified carriers with enhanced mechanical robustness). We systematically investigated the dynamic deformation and transport behavior of these microvesicles under the synergistic effects of geometric constraints, membrane mechanical properties, and external hydrodynamic forcing. Through a series of numerical simulations, we identified a consistent two-stage deformation mechanism, characterized by inlet stretching followed by outlet contraction, as microvesicles traverse constricted microchannel segments. Furthermore, a quantitative correlation was established between the maximum elongation index (EI) and the dimensionless confinement parameter \lambda , defined as the ratio of the initial vesicle diameter to the narrow channel diameter. Notably, our results demonstrate that the Mv-FMM exhibits a superior ability to undergo substantial shape adaptation, forming a streamlined elongated morphology that significantly facilitates its transit through narrow passages. As a result, the critical hydrodynamic force required for the Mv-FMM to pass through such constrictions is markedly lower than that for the Mv-VNM, particularly under high confinement conditions. These findings not only advance the fundamental understanding of soft microparticle transport under confinement but also offer valuable theoretical foundations and simulation-based guidance for the rational design and performance optimization of next-generation targeted drug delivery systems.