A new theoretical model is presented to study the nanoscale electronic inhomogeneity in high-$T_c$ cuprates. In this model, we argue that the randomly distributed out-of-plane interstitial oxygen dopants induces locally the off-diagonal (i.e., hopping integral) disorder. This disorder modulates the superexchange interaction resulting from a large-$U$ Hubbard model, which in turns changes the local pairing interaction. The microscopic self-consistent calculations shows that the large gap regions are registered to the locations of dopants. Large gap regions exhibit small and broader coherence peaks. These results are qualitatively consistent with recent STM observations on optimally doped Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$.