Interlayer interactions are one of the crucial parameters of two-dimensional (2D) layered materials-based junctions. Understanding the limits of interlayer coupling and defining the “maximum building block thickness” in artificially stacked 2D layered materials are key tasks that hold significant importance, not only in fundamental physics, but also in practical applications such as electronics, photonics, and optoelectronics. Here, the interlayer coupling limits are optically investigated of a model 2D layered semiconductor, MoS2, revealing the evolution of distinct interaction mechanisms between layers via artificial stacking. As the total thickness increases, a reduction in the stacking angle influence on the properties of the homojunctions is reflected in the photoluminescence and second harmonic generation responses. The results show that the effective coupling limit for vertically stacked 2D metamaterials resides in three-layer flakes. The findings pave the way to advanced and complex devices of 2D superlattices for photonics and optoelectronics.