The Conductor on round core (CORC) refers to a circular cable that is helically wound with rare-earth-barium-copper-oxide ((RE)BCO) high-temperature superconducting (HTS) tapes. This type of cable finds extensive applications in large superconducting magnets. However, the mechanical–electrical performance of CORC cables is hindered by microscopic edge cracks that occur during the mechanical slitting process of HTS tapes. In this paper, the mixed-mode stress intensity factor (SIF) of cracks in CORC cables under different loading conditions is investigated using the extended finite element method (XFEM). The design variables of CORC cables are optimized by considering the effect of various factors such as the crack parameter, the winding angle, the core radius, and the Poisson’s ratio of the winding core on the SIF. The results indicate that the impact of each factor on the mixed-mode SIF varies depending on the loading mode. Notably, the influence of the winding angle on the SIF is particularly significant and intricate. In the case of tensile loading, a smaller winding angle proves advantageous in impeding crack propagation. Conversely, the most dangerous winding angle for torsional loads is 45°. The divergence of these effects can be indirectly indicated by theoretical solutions regarding the tape strain along the helix direction. For the cases examined, the results have shown that the crack propagation path is independent of these factors, and the direction of propagation is perpendicular to the edge of the tape.