This article communicates the thermal performance, heat transfer rate, and friction factor of Al2O3/DI water nanofluids at different concentrations in a micro-finned tube with tube helical inserts for different twist ratios. The thermal performance, heat transfer coefficient, and friction of the present study is also compared with a plain tube for validation. From the study, it is identified that the micro-finned tube with tube insert performance is higher as compared with a plain tube. Similarly, an empirical relation for Nusselt number (Nu) and friction factor (f) is estimated for straight twisted tube and left-right combination. The deviation between experimental and theoretical values for left-right twist and straight twist is found as 3 and 7% for Nusselt number and 7 and 9% for friction factor, respectively. Similarly, while analyzing the thermal performance, it was found that the maximum performance achieved was with a micro-fin tube with left-right twist with nanofluid concentration of 0.2%.