This study focuses on the innovative integration of different cooling techniques to maximize the thermal performance in a 3D microchannel heat sink (MCHS). The paper discusses nanofluid flow and thermal fields in the MCHS with protrusions subjected to double synthetic jets (SJs). A validated multiphase mixture model is used to study the effect of Al2O3 particles in water. The effect of particle concentration, orifice spacing, orifice height, oscillation frequency, membrane amplitude, and phase actuation on convective and conductive heat transfer is analyzed. Heat transfer is significantly influenced by the particle concentration in both active and inactive SJs. Overall, 180 out-of-phase jet configurations show better performance in terms of convective heat transfer, while in-phase jet arrangements are more efficient in conductive heat transfer enhancement. In terms of thermal performance, 180 out-of-phase cases show a higher figure of merit (FOM) than in-phase SJs. Increasing the frequency and amplitude enhances the heat transfer. In the case of nanofluids, the maximum degree of convective enhancement of 1.23 demonstrates the effectiveness of SJs and protrusions. However, the maximum degree of overall thermal enhancement of 54% is obtained at in-phase actuation under the same conditions.