As an important feature of cutting tools, flutes determine rake faces of their cutting edges, their rigidity, chip breaking, and chip space. In industry, flutes are often ground with standard wheels of simple shape (e.g., 1A1 or 1V1 wheels), resulting in flutes without much variation. To make flutes of more complex shape, standard wheels of complex shape (e.g., 1B1, 1E1, 1F1, and 4Y1 wheels), compared to the current ones, should be used. Unfortunately, current commercial software cannot calculate the locations and orientations of these wheels; this is why they are not used to machine flutes. Moreover, grinding wheels are gradually worn out in use, and the flutes lose accuracy accordingly. Therefore, locations and orientations of the worn wheels should be recalculated or compensated in machining; however, no such technique is currently available. To address this challenge, a generic and efficient approach to determining the locations and orientations of complex standard and worn wheels for cutter flute grinding is proposed in this work. First, a parametric equation of the generic wheel surface and its kinematic equation in five-axis flute grinding are rendered. Second, virtual grinding curves are proposed and defined to directly represent the relationships between wheel location and orientation and the flute profile in a geometric way. Then, the characteristics of the virtual grinding curves are investigated and formulated, and a new model of the generic wheel location and orientation is established. Compared to the existing comparative model, this model significantly increases solution liability and computation efficiency. Finally, three practical cases are studied and discussed to validate this approach. This approach can be used to make flutes of more complex shape and can increase flute accuracy by compensating the locations and orientations of worn wheels in machining.