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Abstract In this work, we investigate the existence and uniqueness properties of a composite structure (multilayered)–fluid interaction PDE system which arises in multi-physics problems, and particularly in biofluidic applications related to the mammalian blood transportation process. The PDE system under consideration consists of the interactive coupling of 3D Stokes flow and 3D elastic dynamics which gives rise to an additional 2D elastic equation on the boundary interface between these 3D PDE systems. By means of a nonstandard mixed variational formulation, we show that the PDE system generates a$$C_0$$ $C_0$-semigroup on the associated finite energy space of data. In this work, the presence of the pressure term in the 3D Stokes equation adds a great challenge to our analysis. To overcome this difficulty, we follow a methodology which is based on the necessarily non-Leray-based elimination of the associated pressure term, via appropriate nonlocal operators. Moreover, while we express the fluid solution variable via decoupling of the Stokes equation, we construct the elastic solution variables by solving a mixed variational formulation via a Babuska–Brezzi approach.