A three-dimensional multiscale modeling framework is developed to analyze the failure procedure of radially aligned zinc oxide (ZnO) enhanced single fiber composites (SFC) under tensile loading to understand the interfacial improvement between the fiber and the matrix. The model introduces four levels in the computational domain. The nanoscale analysis calculates the size-dependent material properties of ZnO nanowires. The interaction between ZnO nanowires and the matrix is simulated using a properly designed representative volume element at the microscale. At the mesoscale, the interface between the carbon fiber and the surrounding area is modeled using the cohesive zone approach. A combination of ABAQUS Finite element software and the failure criteria modeled in UMAT user subroutine is implemented to simulate the single fiber fragmentation test (SFFT) at the macroscale. The numerical results indicate that the interfacial shear strength of SFC can be improved up to 99% after growing ZnO nanowires on the fiber. The effect of ZnO nanowires geometries on the interfacial shear strength of the enhanced SFC is also investigated. Experimental ZnO nanowires enhanced SFFTs are performed on the fabricated samples to validate the results of the developed multiscale model. A good agreement between the numerical and the experimental results was observed.