Rationally designing and precisely constructing the dimensions, configurations and compositions of organic nanomaterials are key issues in material chemistry. Nevertheless, the precise synthesis of organic heterostructure nanomaterials remains challenging owing to the difficulty of manipulating the homogeneous/heterogeneous-nucleation process and the complex epitaxial relationships of combinations of dissimilar materials. Herein, we propose a hierarchical epitaxial-growth approach with the combination of longitudinal and horizontal epitaxial-growth modes for the design and synthesis of a variety of organic superstructure microwires with accurate spatial organisation by regulating the heterogeneous-nucleation crystallisation process. The lattice-matched longitudinal and horizontal epitaxial-growth modes are separately employed to construct the primary organic core/shell and segmented heterostructure microwires. Significantly, these primary organic core/shell and segmented microwires are further applied to construct the core/shell-segmented and segmented-core/shell type's organic superstructure microwires through the implementation of multiple spatial epitaxial-growth modes. This strategy can be generalised to all organic microwires with tailored multiple substructures, which affords an avenue to manipulate their physical/chemical features for various applications.