Synergetic damage under combined blast and fragment loading drives innovational design of protective structures. In present study, sandwich panel with armored hybrid core was designed, fabricated and finally tested under combined blast and fragment loading. The failure behaviors and the underlying mechanisms were analyzed for the components of sandwich panel. The sandwich panel displayed superior performance over equivalent solid plate. The designability of special interest was exploited by elaborating the effects of face sheet configuration, core material and core sequence on the failure behaviors. Experimental results demonstrate that the same thickness of the front and back faces is beneficial for the constraint of back face deflection. The aluminum foam and ultra-high molecular weight polyethylene (UHMWPE) laminate, adopted as the components of armored hybrid core, cooperated well against combined blast and fragment loading by suffering crushing erosion failure and global bulge deformation, respectively. The potential of armored hybrid core is strongly associated with the core sequence. The ceramic layer supported by the material with high stiffness and the protection of upper bulletproof material for UHMWPE laminate layer would benefit the performance of whole panel. The optimal design of core sequence could markedly reduce back face deflection and even avoid the petalling failure of back face.