Polymerization-induced self-assembly (PISA) has become widely recognized as a robust and efficient route to produce nanostructured systems toward functionally superior materials. Herein, by combining mesoscale simulations and micromechanical modeling, we report the structural control over the interfacial organization and the resulted micro mechanical behaviors of novel nanocomposites designed based on the PISA of initiator-modified Janus nanoparticles in diblock copolymers. Our simulations demonstrate that the off center distribution of these functionalized Janus nanoparticles with respect to phase interface can be precisely regulated by tuning the reaction kinetics and the concentration of monomers dispersed in polymer microdomains. Theoretical calculation reveals that such polymerization-induced interfacial self assembly of Janus nanoparticles is fundamentally attributed to a unique entropy effect mediated by the reaction. The diffusion dynamics of monomers in the entanglement mesh of the diblock copolymers is also examined to evaluate the efficiency of the structural control governed by polymerization in the polymer matrix. Furthermore, the combination of techniques allows us to determine how the interfacial polymerization of Janus nanoparticles influences the micromechanical behaviors, such as the elastic fields, modulus, and failure, fracture behaviors of the nanocomposites. The findings have a bearing on enriching our understanding on the thermodynamic nature of polymer nanocomposites and suggest design guidelines for creating block copolymer-based functional materials of programmable interfacial nanostructures correlated with controlled mechanical performance.