In an attempt to investigate the acoustic resonance effect of serpentine passages on internal convection heat transfer, the present work examines a typical high pressure turbine (HPT) blade internal cooling system, based on the geometry of the NASA E3 engine. In order to identify the associated dominant acoustic characteristics, a numerical finite-element method (FEM) simulation (two-step frequency domain analysis) is conducted to solve the Helmholtz equation with and without source terms. Mode shapes of the relevant identified eigenfrequencies (in the 0–20 kHz range) are studied with respect to induced standing sound wave patterns and the local node/antinode distributions. It is observed that despite the complexity of engine geometries, the predominant resonance behavior can be modeled by a same-ended straight duct. Therefore, capturing the physics observed in a generic geometry, the heat transfer ramifications are experimentally investigated in a scaled wind tunnel facility at a representative resonance condition. Focusing on the straight cooling channel's longitudinal eigenmode in the presence of an isolated rib element, the impact of standing sound waves on convective heat transfer and aerodynamic losses are demonstrated by liquid crystal thermometry, local static pressure and sound level measurements. The findings indicate a pronounced heat transfer influence in the rib wake separation region, without a higher pressure drop penalty. This highlights the potential of modulating the aerothermal performance of the system via acoustic resonance mode excitations.