This article reports on work toward developing a practical methodology for the predictive modeling of the performance of thermoplastic composite (TPC) sandwich structures under impact loading. Explicit finite element analysis methods, using LS-DYNA® software, are described. Details of extensive materials characterization tests and material model parameter calibration for both the composite skin and polymer foam core are included. The simulations of deformation response, damage and failure of the sandwich structures is validated against experimental tests of the indentation and three-point bending of TPC sandwich beams. Good agreement between simulations and experiments has been achieved for indentation loading up to high degrees of core crush. The same is true for a significant part of the bending response including failure prediction. However, it has been necessary to introduce a principal strain fracture criterion to account for core shear and skin—core debonding failures at higher strains. For full predictive capability in this region, further experimental work is needed to obtain the necessary strain rate-dependent fracture data for the core and interface.