Multi-material Additive manufacturing (AM) has opened new opportunities for the creation of multifunctional structures that enables value-added structural product designs. Among the multi-material AM techniques, multi-nozzle fused filament fabrication which is a type of material extrusion technique is found to be the more popular choice for multi-material polymer fabrication. One major challenge of multi-material additive manufacturing of polymers is the poor mechanical strength at the interface of the dissimilar materials such as polylactic acid (PLA) and thermoplastic polyurethane (TPU) due to the lack of chemical affinity. Therefore, understanding the mechanical strength at the interface of these dissimilar materials becomes an important topic as it allows product designers to do necessary tweak to the design to compensate for the weaker link in the structural design. In this work, we investigated the tensile strength and the shear strength of different combinations of PLA and TPU and their respective nanocomposites, as well as the fatigue analysis of the bi-layer structures made of these dissimilar materials in a 3-point bending test configuration. Generally, when functional fillers or particles are added to the polymer in composites, they tend to adversely affect the interlaminar adhesion property and fatigue life of the soft-rigid bilayer structure. It was found, that the interlaminar tensile strength and the interlaminar shear strength can reduce as high as 44% and 78%, respectively, compared to the baseline samples with no fillers.