Heat exchangers are among the most applied energy systems and increasing their performance can contribute to resolving current energy and environmental issues. Of the active and passive methods of heat transfer enhancement, air bubble injection and using nanofluids, respectively, were selected for this research. Experiments were conducted to study energy, exergy and hydrodynamic performances of a vertical double pipe heat exchanger under the effects of the combined method applied in the annulus side. Finally, multi-objective optimization based on artificial neural network metamodeling and genetic algorithm was carried out to find the best performance on the basis of heat exchanger effectiveness and exergy performance. Results indicate a promising potential in performance enhancement of the combined method.