This study investigates the coupled effects of mechanical vibration on heat transfer and entropy generation in non-Newtonian nanofluid flow under constant wall temperature conditions. The introduction of vibration promotes radial mixing and temperature uniformity, leading to a marked increase in convective heat transfer. Parametric analysis reveals that amplitude is the most influential factor, followed by frequency, Reynolds number, and nanoparticle concentration. Increasing vibration amplitude consistently enhances the Nusselt number across all Reynolds numbers, with values rising from approximately 38–118 in the static case to 202–224 at 4 mm amplitude and 100 Hz. The frequency effect becomes more prominent at higher amplitudes, with optimal enhancement observed between 25–100 Hz. Entropy-based analysis shows that vibration reduces total irreversibility by mitigating thermal gradients; however, excessive vibration can elevate viscous dissipation, increasing entropy generation. Thus, optimal thermal performance is achieved at moderate amplitudes and relatively high frequencies, balancing enhanced heat transfer with minimized entropy production. Two-phase numerical modeling accurately captures nanoparticle slip, diffusion, and clustering effects, exhibiting better agreement with experimental data than single-phase models. The findings provide valuable insights for the design and optimization of nanofluid-based thermal systems operating under vibrational environments.