The thermodynamic relations of exergy efficiency, exergy destruction, thermal and friction entropy generation, Bejan number, and collector efficiency was evaluated experimentally by considering water-based nanodiamond (ND) nanofluids circulating in a flat plate collector (FPC) at different particle loadings (φ = 0.2% to φ = 1.0%) and Reynolds number (5000-13,000). Additionally, heat transfer, pumping power, and friction factor was also evaluated. Thermophysical properties were measured experimentally and developed regression correlation models to obtain the thermal conductivity, viscosity, specific heat, and density of nanofluids. Experiments indicate that the collector thermal efficiency for water is 53%; however, it is increased to 74% for 1.0% volume concentration of ND/water nanofluid in the FPC. The exergy efficiency is increased to 7.21%; exergy destruction and thermal entropy generation is decreased to 5.14% and 5.81%, and the frictional entropy generation is increased to 23% at 1.0% particle loading and Reynolds number of 10,098.1, against the water data. The Nusselt number is enhanced to 32.31% at 1.0% vol. concentration of nanofluid at Reynolds number of 10,098.1, with friction factor penalty of 26.77% compared to water. Furthermore, collector cost, energy, and environmental analyses are also performed for water and ND/water nanofluids. Relevant regression equations are proposed to evaluate the Nusselt number and friction factor. © 2021 by Begell House, Inc. www.begellhouse.com