There is a significant enhancement of the heat transfer rate with the usage of nanofluid. This article describes a study of the combination of using nanofluid with inserts, which has proved itself in attaining higher benefits in a heat exchanger, such as the radiator in automobiles, industries, etc. Nanofluids are emerging as alternative fluids for heat transfer applications due to enhanced thermal properties. In this paper, the thermal hydraulic performance of ZrO2, awater-based nanofluid with various volume concentrations of 0.1%, 0.25%, and 0.5%, and staggered conical strip inserts with three different twist ratios of 2.5, 3.5, and 4.5 in forward and backward flow patterns were experimentally tested under a fully developed laminar flow regime of 0–50 lphthrough a horizontal test pipe section with a length of 1 m with a constant wall heat flux of 280 W as the input boundary condition. The temperatures at equidistant position and across the test section were measured using K-type thermocouples. The pressure drop across the test section was measured using a U-tube manometer. The observed results showed that the use of staggered conical strip inserts improved the heat transfer rates up to that of 130.5%, 102.7%, and 64.52% in the forward arrangement, and similarly 145.03%, 116.57%, and 80.92% in the backward arrangement with the twist ratios of 2.5, 3.5, and 4.5 at the 0.5% volume concentration of ZrO2 nanofluid. It was also seen that the improvement in heat transfer was comparatively lower for the other two volume concentrations considered in this study. The twist ratio generates more swirl flow, disrupting the thermal hydraulic boundary layer. Nanofluids with a higher volume concentration lead to higher heat transfer due to higher effective thermal conductivity of the prepared nanofluid. The thermal performance factor (TPF) with conical strip inserts at all volume concentrations of nanofluids was perceived as greater than 1. A sizable thermal performance ratio of 1.62 was obtained for the backward-arranged conical strip insert with 2.5 as the twist ratio and a volume concentration of 0.5% ZrO2/deionized water nanofluid. Correlations were developed for the Nusselt number and friction factor based on the obtained experimental data with the help of regression analysis.