A thermo-acoustic engine is a device converting thermal energy into high amplitude acoustic waves that can be harvested, for example, to obtain electricity. The core of the device is a stack/regenerator along which a temperature gradient is created using one hot and one cold heat exchanger. Correctly designed, the thermal interaction between the working fluid and the regenerator assists in amplifying incident acoustic waves. Previous studies have indicated good efficiency obtained with a system of low geometrical complexity. However, for the practical application of this technique it is vital to understand and identify critical design parameters and operating conditions. This is of special interest in automotive applications where the operating conditions vary significantly over a drive cycle. This works aims at providing a framework for studying the net power generation over a drive cycle. First, an engineering non-linear model for the efficiency of the thermo-acoustic engine is established. It is based on low-order acoustic networks that have the advantage of being computationally effective and allows for individual optimization of components. This model is then used to loop over a drive cycle of a typical commercial vehicle, while also accounting for pump losses given by the heat exchange processes. Although an engine not optimized for the present problem was used, promising performance, with a thermal efficiency of 7%, was found. Also the importance of adapting the engine to the varying operating conditions over the drive cycle was illustrated.