It is known that copolymers are critical in modifying interfaces of multilayered polymeric products. However, not much is known about the influence of the macromolecular architecture of copolymers on the interfacial morphology evolution, viscoelasticity, and processability of layered systems. Therefore, we demonstrate the role of macromolecular architecture of copolymers at layer-layer interfaces of multilayered polymers from the equilibrium to flow conditions, based on a combined morphological and rheological investigation. Intriguingly, in comparison to a pure grafting case, the formation of interfacial copolymers of a complex grafting architecture of a branching and cross-linking mixture substantially increases the overall viscosity. With a higher grafting density of copolymers of such an architecture, layer-layer interfaces become more corrugated upon reaction. Particularly, under real coextrusion processing flows, with these copolymers, interfacial roughness and irregularities are further amplified in the die exit as compared to that in the feedblock because of the accelerated reaction kinetics by the compressive flow field. Besides, the configuration of copolymers containing a mixture of branched and cross-linked chains at the interface significantly hinders the structural stress relaxation process and resists the interfacial slip. Under fast extensional flows, multilayered films display an unexpected strain-hardening behavior with a strong dependence on the number of layers, arising from the interfacial stitching and elastic network formed with copolymers of the complex architecture. These findings will enable the better understanding of copolymer architectures in the control of interfaces of multilayered films with improved flow stability and macroscopic properties.