In the present study, numerical simulations have been carried out on thermal characteristics and second-law analysis of turbulent Cu–H2O nanofluid flow with the nanoparticle volume fraction of 0<ϕ<1.5% inside heat exchangers fitted by transverse-cut twisted tapes (TCTTs) with alternate axis. The transverse-cut ratios are in the range of 0.7 < b/c < 0.9 and 2 < s/c < 2.5, and the Reynolds number is varied between 5000 and 15,000. The impacts of the design variables on the turbulent kinetic energy, temperature distribution, thermal and frictional entropy generations and Bejan number have been evaluated. The simulations show that the TCTTs with b/c = 0.7 generate higher turbulent kinetic energy compared to the b/c = 0.9 due to higher swirl generation and flow disturbance. The additional recirculating flow produced near the alternate edges is another main physical factor for heat transfer augmentation. It is found that raising the nanoparticles volume concentration reduces the thermal entropy generation which is attributed to the thermal conductivity enhancement of nanofluids. Besides, raising the nanoparticles volume concentration from 0 to 1.5% reduces the Ng,thermal by 23%.