Plate Fin Heat Sinks (PFHS) are among the simplest and most widespread devices for electronics cooling. Because of the many design parameters to be considered, developing both cost and thermal effective PFHS is a critical issue. Here, a novel thermal model of PFHS is presented. The model has a broad field of applicability, being comprehensive of the effects of flow bypass, developing boundary layers, fin efficiency and spreading resistance. Experiments are then carried out to validate the proposed thermal model, and its good accuracy is demonstrated. Finally, an optimization methodology based on genetic algorithms is proposed for a cost-effective selection of the design parameters of PFHS, which is particularly effective with semi-active configurations. Such an optimization methodology is then tested on a commercial heat sink, resulting in a possible 53% volume reduction at fixed thermal performances.