Abstract The heterointegration of graphene with semiconductor materials and the development of graphene‐based hybrid functional devices are heavily bound to the control of surface energy. Although remote epitaxy offers one of the most appealing techniques for implementing 3D/2D heterostructures, it is only suitable for polar materials and is hugely dependent on the graphene interface quality. Here, the growth of defect‐free single‐crystalline germanium (Ge) layers on a graphene‐coated Ge substrate is demonstrated by introducing a new approach named anchor point nucleation (APN). This powerful approach based on graphene surface engineering enables the growth of semiconductors on any type of substrate covered by graphene. Through plasma treatment, defects such as dangling bonds and nanoholes, which act as preferential nucleation sites, are introduced in the graphene layer. These experimental data unravel the nature of those defects, their role in nucleation, and the mechanisms governing this technique. Additionally, high‐resolution transmission microscopy combined with geometrical phase analysis established that the as‐grown layers are perfectly single‐crystalline, stress‐free, and oriented by the substrate underneath the engineered graphene layer. These findings provide new insights into graphene engineering by plasma and open up a universal pathway for the heterointegration of high‐quality 3D semiconductors on graphene for disruptive hybrid devices.