The selection of a wheel profile is a topic of great interest as it can affect running performances and wheel wear, which needs to be determined based on the actual operational line. Most existing studies, however, aim to improve running performances or reduce contact forces/wear/rolling contact fatigue (RCF) on curves with ideal radii, with little attention to the track layout parameters, including curves, superelevation, gauge, and cant, etc. In contrast, with the expansion of urbanization, as well as some unique geographic or economic reasons, more and more railway vehicles shuttle on fixed lines. For these vehicles, the traditional wheel profile designing method may not be the optimal choice. In this sense, this paper presents a novel wheel profile designing method, which combines FaSrtip, wheel material loss function developed by University of Sheffield (USFD function), and Kriging surrogate model (KSM), to reduce wheel wear for these vehicles that primarily operate on fixed lines, for which an Sgnss wagon running on the German Blankenburg–Rübeland railway line is introduced as a case. Besides, regarding the influence of vehicle suspension characteristics on wheel wear, most of the studies have studied the lateral stiffness, longitudinal stiffness, and yaw damper characteristics of suspension systems, since these parameters have an obvious influence on wheel wear. However, there is currently little research on the relationship between the vertical suspension characteristics and wheel wear. Therefore, it is also investigated in this paper, and a suggestion for the arrangement of the vertical primary spring stiffness of the Y25 bogie is given.