This study explores the efficacy of cerium introduction, both on its own and in combination with nickel, into PrBaMn2O5+δ (PBM) structures to enhance solid oxide fuel cell (SOFC) anodes. We synthesized Pr1–xCexBaMn2O5+δ compositions for x values of 0.05 (PrCe5) and 0.1 (PrCe10), as well as a nickel-doped variant (PrCe5Ni), assessing their performance under H2–3% H2O reducing conditions pertinent to SOFC anode operations. Our findings reveal that the PrCe5 composition exhibits a thermal expansion coefficient (TEC) that not only improves upon that of the Ce-free counterpart but also aligns closely with the TEC standards of prevalent SOFC electrolytes. A notable advancement was achieved with the application of a 3.5 μm gadolinia-doped ceria (GDC) buffer layer through physical vapor deposition, effectively mitigating chemical interactions between PBM-based anodes and yttria-stabilized zirconia (YSZ) electrolytes, a concern highlighted by in situ neutron diffraction analyses. Electrochemical impedance spectroscopy, conducted over 220 h in a H2–3% H2O atmosphere at 750 °C, demonstrated that the optimal 3.5 μm thickness of the GDC buffer layer significantly minimizes the area-specific resistance (ASR) degradation rate to 0.002 Ω cm2/h, markedly outperforming both thinner (1 μm) and thicker (8 μm) GDC layers, which showed higher degradation rates of 0.15–0.2 Ω cm2/h due to the diffusion of Ba ions or delamination. Moreover, cerium doping fosters superior microstructural stability and obviates barium diffusion, thereby suggesting an enhanced durability of the doped anodes over their lifespan. Integrating nickel into the PrCe5 structure halved the ASR to 0.5 Ω cm2 at 750 °C, situating it well within the ideal performance range for SOFC anodes. The enhancement brought about by simultaneously doping PBM with cerium and nickel, which fundamentally relies on the critical contributions of defect chemistry and crystal structure, highlights the significance of these fields in creating sophisticated materials for energy related applications.