A cost-effective alternative for lowering carbon emissions from building heating is the use of flat-plate solar collectors (FPSCs). However, low thermal efficiency is a significant barrier to their effective implementation. Favorable nanofluids’ thermophysical properties have the potential to increase FPSCs’ effectiveness. Accordingly, this study evaluates the performance of an FPSC operating with Fe3O4-water nanofluid in terms of its thermo-hydraulic characteristics with operating parameters ranging from 303 to 333 K for the collector inlet temperature, 0.0167 to 0.05 kg/s for the mass flow rate, and 0.1 to 2% for nanoparticles’ volume fraction, respectively. The numerical findings demonstrated that under identical operating conditions, increasing the volume fraction up to 2% resulted in an improvement of 4.28% and 8.90% in energy and energy efficiency, respectively. However, a 13.51% and 7.93% rise in the friction factor and pressure drop, respectively, have also been observed. As a result, the performance index (PI) criteria were used to determine the optimal volume fraction (0.5%) of Fe3O4 nanoparticles, which enhanced the convective heat transfer, exergy efficiency, and energy efficiency by 12.90%, 4.33%, and 2.64%, respectively.