•A multiscale framework is proposed to predict the fracture toughness enhancement of polymer nanocomposites.•The effect of strain rate and interfacial characteristic on fracture toughness is studied.•Interfacial debonding and subsequent plastic void growth are considered as toughening mechanisms.•The toughening mechanisms are described progressively in the fracture process.•The fracture toughness is dependent on interfacial characteristics and decreases with increasing strain rate. We propose a multiscale framework to predict the fracture toughness enhancement in polymer nanocomposites at various strain rates considering the interfacial debonding and subsequent plastic yielding of the matrix mechanisms. The elasto-plastic behavior of pure polymer and polymer nanocomposite is characterized at different strain rates via molecular dynamics simulation, and the fracture toughness enhancement are computed using a multiscale bridging approach via the finite element simulation and linear elastic fracture mechanics. The predicted results show that the toughness enhancement is affected by the strain rate and interfacial characteristics, and that it agrees well with the experimental results. These findings is expected to provide guidelines for predicting the fracture toughness of nanocomposites under various strain rate conditions, as well as insights into the customization of interfacial characteristics for the target toughness.