Recently, high-strength zirconia-toughened alumina (ZTA) ceramic substrates have attracted interest, because they offer much improved mechanical properties over straight alumina, while maintaining advantages such as good thermal conductivity and chemical stability. This allows their application in high-power electronics and piezoresistive thick-film sensors, where the substrate is subjected to considerable stress. This work examines the impact of processing a range of thick film materials (Ag- and Au-based conductors, and a resistor material widely used in piezoresistive sensors) on the short- and long-term strength of ZTA, as compared to the standard 96% alumina used in thick-film electronics. It is found that many layers substantially reduce the substrate strength, especially in the long term, which is related to enhanced crack growth in the presence of glassy layers. These findings have pronounced implications in piezoresistive sensor design.