It has been well documented how spatial inhibition of return (IOR) interacts with executive functions in a two-dimensional plane, i.e., significantly decreased interference at the cued (inhibited) compared to the uncued location. It remains unknown, however, how spatial IOR interacts with executive functions along the depth dimension of the real 3D world. Here, we adapted the Posner spatial-cuing paradigm into a virtual 3D world. The location-based IOR was orthogonally combined with the flanker effect: The target and its flanker could appear at either the cued or the uncued location in a closer or farther depth plane. Moreover, the flanker effect was differentiated into the pre-response and response levels, and the flankers could appear in the either same (Experiment 1) or different (Experiment 2) depth plane from the target. A simple detection task was also adopted to test the pure effect of how visuospatial attention is prevented from returning previously attended location along the depth dimension. The results showed that there existed significant IOR effects only when target was presented in the farther depth plane. Moreover, significantly reversed response-level conflicts were observed at the cued location in the farther depth plane, indicating that spatial IOR toward the farther depth plane was more than a simple effect of attentional orienting. Rather, the inhibitory tagging mechanism may take place. In addition, orienting to the close depth plane resulted in either a facilitatory or null effect. Accordingly, only the pre-response-level conflict was modulated by attentional orienting to the closer depth plane.