In this paper, we devise an approach for material selection of constituent layers of a composite piezoresistive cantilever sensor using Ashby’s methodology. A rational choice of the constituent materials of a piezoresistive cantilever sensor becomes critical not only due to its multi-layered hetero structure but also due to the interdependence of material properties and geometrical parameters in governing its performance and reliability. Material selection is performed by identifying the performance metrics that govern the sensor performance and depict the interplay between the material constants and geometrical parameters. Here, apart from considering the coupled effects of electro-mechanical parameters we have also incorporated the impact of joule heating induced self-heating effects in the material selection process. Further, the material selection process is validated by computing the performance metrics of different sensors with same resonant frequency using analytical models. Results show that a silicon cantilever with a doped p-type piezoresistor, a silicon dioxide isolation layer and a gold immobilization layer is relatively better considering performance characteristics and reliability as compared to an SU-8 polymeric and other solid-state semiconductor based piezoresistive cantilever surface stress sensors, especially when joule heating induced inaccuracy is taken into account. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.