This paper investigates the adaptability of different Reynolds-averaged Navier-Stokes (RANS)-based turbulence models for flow behavior and thermal performance of combined multiple shell-pass shell and tube heat exchanger (CMSP-STHE) with unilateral ladder-type helical baffle (ULHB). The presence of ULHB in the outer shell pass of the heat exchanger leads to a complex flow configuration and makes it quite challenging to deal with its computational analysis. The computational fluid dynamic method compares the CMSP-STHE with ULHB with the traditional shell and tube heat exchanger with segmental baffles (SG-STHE). The performance of four turbulence models, namely, realizable k–ɛ, standard k–ɛ, standard k–ω and RNG k–ɛ models are compared with the correlation data. It is observed that the standard k–ω turbulence model more accurately predicts the heat transfer and pressure drop compared to other models. The logarithmic mean temperature difference (LMTD) results for various mass flowrates and thermal performance enhancement factor (TPEF) corresponding to various values of Re are also presented. It is concluded that the TPEF of CMSP (ULHB)-STHE is higher than that of the conventional STHE. The average enhancement is approximately 28% for ULHB STHE than the conventional one. Further, variations in velocity, turbulence kinetic energy, and local Nusselt number along the tube length are examined to understand the thermal performance behavior with CMSP (ULHB)-STHE. It is clear from the results that the CMSP (ULHB)-STHE is a better alternative to the traditional SG-STHEs.