Heat exchangers are key equipment for energy conversion and utilization, and enhancing the heat transfer coefficient while reducing energy consumption is a core objective of heat exchanger design. This article focuses on the mechanism of irreversible loss caused by heat transfer and flow resistance in tube bundle heat exchangers. Based on the second law of thermodynamics, a local entropy production analysis model is established, which includes average entropy production, turbulent entropy production, wall entropy production, and heat transfer entropy production. The flow and heat transfer characteristics as well as the distribution laws of each entropy production are obtained for both in-line and staggered tube bundle arrangements, and the influence of tube bundle arrangement on the irreversibility of flow and heat transfer is quantitatively analyzed. The research results indicate that turbulent entropy production and heat transfer entropy production are the main components of total entropy production in heat exchangers, and they are mainly distributed in the near-wall region and the wake region where flow separation occurs. As the gas velocity increases, the average entropy production, turbulent entropy production, and wall entropy production gradually increase, while the heat transfer entropy production gradually decreases. Different tube bundle arrangements correspond to different optimal flow rates, at which the total entropy production of the flow and heat transfer process can be minimized. When the gas velocity is relatively low, the staggered tube bundle arrangement is recommended, because it can effectively reduce the total entropy production of the system and minimize irreversible losses. In contrast, when the gas velocity is relatively high, the in-line tube bundle arrangement should be selected.