A three-dimensional computational fluid dynamics model with the thermal phase change model is used to investigate the thermal–hydraulic characteristics of a steam generator with and without quatrefoil tube support plates. The two types of modeled designs are a unit pipe with and one without tube support plates. The computational fluid dynamics simulations capture the boiling phenomena, vortex and recirculation distributions, and the periodic characteristics of the circumferential wall temperature in the regions surrounding the tube support plates. The cross-flow energy responsible for flow-induced vibration damage in the region of the U-bend tubes is obtained with the aid of these localized thermal–hydraulic distributions. A comparison between the key parameters of the unit pipe models with and without tube support plates clearly reveals the influence of tube support plates in guiding flow behavior and alleviating flow-induced vibration damage for a steam generator’s U-bend tube bundle. Therefore, this computational fluid dynamics model can provide technical support for optimizing tube support plate design and improving the thermal–hydraulic characteristics of steam generator.