The microchannel heat exchanger is one of the most compact and effective heat exchangers used for cooling devices in building air conditioning system, while application of nanofluids in microchannel further enhance its thermal performance due to its much higher thermal conductivity. Considering the continuous rapid increase in energy consumption in the building sector, especially in air conditioning systems, the heat transfer performance of a microchannel with nanofluids should be further enhanced to realize energy savings. This study analyzes the influence of combining nanofluid and flow disturbance structure on the heat transfer enhancement of a microchannel, which is also the noted novelty. A rectangular grooved microchannel (RGMC) is proposed, and its thermal performance using Al2O3/water nanofluids is investigated using the CFD method, with the mixture model to simulate the Al2O3/water nanofluids considering the slip velocity between the base fluid and nanoparticles. The results show that at 1.5 m/s, Nu of RGMC with 2 vol% nanofluids is 38.5% larger than that of smooth microchannel (SMC) with the same nanofluids, and 36.7% larger than that of RGMC with pure water, indicating the much better heat transfer performance of the novel designed RGMC structure. The maximum temperature for RGMC is 5 K lower than SMC with 2 vol% Al2O3/water nanofluid at inlet velocity of 1.5 m/s. Further analysis on the integrated effect between fluid flow and heat transfer shows that the synergy angle β near the center line of RGMC is much lower than that of SMC, representing that the better thermal performance is caused by the flow structured induced by the grooves. Moreover, at 1.5 m/s, βα of SMC with 2 vol% nanofluid is 89.4 Deg, which is 1.66 Deg higher than the βα value of RGMC, while at 0.25 m/s, the βα of two types of microchannel are close to each other. This indicates that the groove structure shows greater enhancement at higher inlet velocity. It is concluded that combining nanofluid and groove structure can significantly enhance heat transfer of the microchannel. The nanofluid enhances heat transfer at lower inlet velocity, while the groove structure enhances it at higher inlet velocity. This study will be helpful for the design of a high-efficiency microchannel heat exchanger that promotes building energy savings.