Interventional catheters are the pivotal components of catheter-assisted intervention therapy. However, the inevitable contact and friction between catheters and complex human channels usually lead to severe patient burdens. A fabrication strategy for variable-stiffness catheters based on time-dependent helical flow was developed by regulating the alignment of titanium dioxide (TiO2) nanorods in polyolefin elastomer (POE) catheters. In particular, the uniaxial and off-axial alignments of the TiO2 nanorods were manipulated to adjust the mechanical properties of each section in the POE catheters, where the processing flow pattern was transformed from axial to helical. To achieve the desired performance in practical applications, two catheters with a programmable helix angle of embedded TiO2 nanorods along the axial direction were designed. Correspondingly, the as-designed catheters displayed remarkably reduced interventional loads (e.g., a maximum reduction of 49.3% and 39.7% in single- and multi-curvature channels, respectively) and an enhancement of 50% in rotation synchronization, indicating promising potential for application in catheter-assisted interventional therapy. This study proposes an effective structuring design strategy for composed catheters with variable-stiffness segments that can be extended to all interventional catheter production techniques.