This study numerically investigates the heat transfer and entropy generation of nanofluid flow under mechanical vibration, employing approved formulations to model the nanofluid density, specific heat, viscosity, and conductivity. Specifically, the impact of vibration on laminar forced convection thermal flow of both pure water and Al2O3-water nanofluid within a pipe is explored using CFD. Various Reynolds numbers are examined under constant heat flux conditions, with nanofluid properties determined using established correlations. Results indicate that applying Al2O3 nanofluid slurry instead of pure water at low Reynolds numbers reduces entropy generation, proving advantageous. Vibration enhances heat transfer by intensifying fluid agitation and promoting particle dispersion near the wall, resulting in a significantly more uniform temperature distribution along the pipe, approximately 100 times more than steady-state flow. Analysis reveals vibration’s effectiveness in reducing irreversibility, especially at lower Reynolds numbers, with substantial enhancements in heat transfer coefficients, up to approximately fivefold compared to steady-state flow, particularly for nanofluid flows. Optimal conditions for maximizing heat transfer enhancement emphasize nanoparticle size and concentration. Mechanical vibration with different frequencies produces significant improvements in heat transfer compared to amplitude variations, primarily influenced by the Reynolds number. Overall, this study offers valuable insights into the intricate relationship between vibration, fluid dynamics, and heat transfer in nanofluid flows, with practical implications for optimizing thermal management systems across various engineering applications.