Thermoelectric generation (TEG) and organic Rankine cycle (ORC) technologies both have their respective limitations in recovering waste heat from ships. However, the combination of TEG and ORC is an effective approach to achieve cascaded waste heat recovery and improve heat utilization efficiency. There has been some progress in research on waste heat recovery in maritime applications based on TEG‐ORC combined cycles. The selection of a working medium is a crucial element that directly influences the design and performance of the entire system, but there is limited research on the impact of different working fluids on combined cycle systems. In this study, a simulation model of a TEG‐ORC combined cycle system was established to examine its output potential using two different working fluids R1234ze and a mixture of R245fa/R1234ze. The results demonstrate that compared to employing the R1234ze working medium, the combined cycle system with the mixed working medium achieved a 13% increase in maximum output power, a 102% improvement in optimum thermal efficiency, and a 53% reduction in optimum power production cost. Additionally, the power output distribution in the system utilizing the mixed working fluid was more uniform compared to the system employing a single working medium. This confirms the great potential of using a mixed working fluid in a combined cycle system.