Scour of pile group foundations is a common hazard for cross-river bridges and can produce considerable damage to piles in earthquake-prone regions. The fragility-based performance assessment for pile group supported bridges subjected to earthquake and scour hazards has drawn increasing attention from engineering practice and academic communities. Such assessment requires numerical models that are computationally efficient and accurate in describing the mechanical behavior associated with the complex soil-pile interaction of these soil-bridge systems. Additionally, selecting an optimal ground motion intensity measure (IM) is generally required for such assessments. However, modeling the pile group effect for seismically excited pile groups and the optimal IM for the scoured bridges have not been well addressed in previous related studies. To this end, a practical pile group effect modeling approach is adopted in this study and validated by a set of shake table tests on scoured pile group bridge available in the literature. Based on the validated numerical modeling approach for the soil pile interaction, a series of coupled soil-bridge models are generated considering the structural and soil parameter uncertainty and analyzed in the OpenSees platform. The optimal IM for various engineering demand parameters (EDPs) is identified from thirty-nine scalar IM candidates through the criteria of efficiency, practicality, sufficiency, and hazard computability. Finally, a straightforward form of probabilistic seismic demand model (PSDM), incorporating the effect of scour depth changes, is developed for pile group supported bridges. Results show that the increase of scour depth significantly increases the curvature demand of a pile group and statistically reduces the embedded depth of the belowground plastic hinge of the pile shaft. The rank of optimal IM candidates directly depends on the selection criteria of an optimal IM and the selection of EDP. In addition, the scour depth slightly affects the rank of optimal IMs. Generally, VSI, PGV, and Sv,1.0 are recommended for the probabilistic seismic demand analysis of pile group supported bridges in sandy soils with scour potentials.