Generation IV reactors, characterized by enhanced safety and efficiency, introduce complex thermo-hydraulic challenges due to novel coolants (e.g., liquid metals, molten salts, supercritical fluids) and multi-physics coupling mechanisms. Computational fluid dynamics (CFD) has emerged as a critical tool for addressing these challenges. In order to comprehensively analyze the application of CFD in Generation IV reactors, identify technical bottlenecks, and propose strategies for future development. A systematic review is conducted across six Generation IV reactor types, i.e., Sodium-cooled Fast Reactor (SFR), Lead-cooled Fast Reactor (LFR), Molten Salt Reactor (MSR), SuperCritical Water Reactor (SCWR), Gas-cooled Fast Reactor (GFR), Very-High Temperature Reactor (VHTR), focusing on CFD applications in component-scale flow analysis, system-level transient simulation, multi-physics coupling, and cross-scale modeling. The special requirements for fine thermal hydraulic modeling and analysis of new working fluids such as liquid metals and molten salts are summarized, and key challenges, including spatiotemporal scale discrepancies, validation uncertainties, and multi-field nonlinear interactions, are analyzed through case studies and technical comparisons. While advancements in multi-scale coupling strategies and hybrid modeling approaches have expanded CFD's predictive capabilities, significant challenges remain, including limitations in turbulence modeling accuracy, computational demands for full-core analyses, and validation gaps under extreme operational conditions. Emerging methodologies that integrate data-driven techniques with traditional physics-based models show promise in overcoming these barriers, though their broader implementation requires standardized validation protocols and improved interoperability across simulation frameworks. These developments highlight CFD's growing role in advancing reactor design while underscoring the need for systematic collaboration to bridge theoretical innovations and industrial applications. Future advancements require synergistic integration of AI-driven surrogate modeling, standardized multi-physics coupling interfaces, and cloud-based collaborative platforms. Establishing technology readiness level (TRL) matrices and open-source toolchains will accelerate the transition of CFD from research to industrial deployment in Generation IV reactor engineering.