Energy efficiency enhancement methods have received considerable attention within the industry and scientific community, owing to the rising concern of global energy sustainability. The present article attempts to scrutinize the effects of electrohydrodynamics and nanofluids on the rate of heat transfer and fluid flow in the 3-D chain microchannels. Improved heat exchangers (e.g., chain microchannel) would have a key role in increasing of the performance of such systems since they provide efficient thermal management needed for more robust computational power. To date, analysis of electrohydrodynamics and nanofluids in the chain microchannel was not comprehensively discussed. Here, steady-state, laminar, and three-dimensional chain microchannel are numerically modeled based on a control volume method in Fluent. Results show that by increasing the volume fraction of nanoparticles, the viscosity of the nanofluid increases leading to an increase in pressure drops. Moreover, Nusselt at Re = 125, 250, 500 and 1000 for hybrid nanofluid (empty set (AL2O3)= empty set (CuO)=4%) is 1.206, 1.541, 2.075 and 2.707, respectively which, in turn, depicts surging by 22.94%, 24.17%, 24.70% and 24.707% in comparison to water, respectively. In addition, at low Reynolds number (0.416 <= Re <= 4.166), the lower Reynolds results in decreasing of percentage of pressure drop. Meanwhile, imposing electrohydrodynamic (V = 30 KV) at Re= 125, 250, 500 and 1000 leads to increasing by 23%, 22%, 20% and 18% of Nusselt number in comparison to absence of electric field, respectively. It means that the considered effect of the increasing the Nusselt number at lower Reynolds number is more effective. Moreover, heat transfer rises with augmentation of supplied voltage and Reynolds number.