In the current investigation, heat, flow characteristics, and exergy analysis of hybrid and single nanoparticles-based water passing through a triple ribbed tube heat exchanger (TRTHE) under several design and operation parameters are studied. A computational fluid dynamics (CFD) modeling is carried out using ANSYS-FLUENT 19 code while the validation criteria are accomplished with experimental data and empirical correlations in the literature. The model technique of 3D re-normalization group (RNG)/k–ϵ with enhanced wall treatment is chosen considering the conjugate heat transfer between the fluids. A user-defined function is utilized to specify the thermophysical properties of nanofluids and water based on the operating fluid temperature. The design and operating nanofluid velocity and temperature of inner, intermediate, and outer tubes are 0.7 m/s at 10 °C, 0.05–0.13 m/s at 70 °C, and 0.05 m/s at 18 °C, respectively. The ribs under consideration are trapezoidal, semi-circular, semi-elliptical, triangular, rectangular, and square-shaped and the tested perforated louver widths are 0.5, 1, 1.5, and 2 mm. Three hybrid combinations of nanomaterials (oxide/oxide, oxide/carbide, oxide/carbon nanotube) by constant volume percent of 50/50% are employed with water as a base fluid under a constant volume concentration of 0.1%. Four different kinds of nanoparticles are chosen as Al2O3, MgO, SiC, and MWCNT in order to perform the present study.The obtained findings manifested that the hybrid nanofluid of Al2O3+MWCNT/H2O achieves a higher heat transfer rate compared with single nanofluids. A lower rib louver width with semi-circular rib geometry and staggered rib arrangement leads to an increase in the Nusselt number and effectiveness of the TRTHE. The use of semi-circular rib shape produces a rise of dimensionless exergy loss rate by about 5.4–21.6% more than other rib shapes.