Copyright © 2018 American Chemical Society. One challenge in studying high-temperature superconductivity (HTSC) stems from a lack of direct experimental evidence linking lattice inhomogeneity and superconductivity. Here, we apply synchrotron hard X-ray nanoimaging and small-angle scattering to reveal a novel micron-scaled ribbon phase in optimally doped Bi2Sr2CaCu2O8+δ (Bi-2212, with δ = 0.1). The morphology of the ribbon-like phase evolves simultaneously with the dome-shaped TC behavior under pressure. X-ray absorption studies show that the increasing of TC is associated with oxygen-hole redistribution in the CuO2 plan, while TC starts to decrease with pressure when oxygen holes become immobile. Additional X-ray irradiation experiments reveal that nanoscaled short-range ordering of oxygen vacancies could further lower TC, which indicates that the optimal TC is affected not only by an optimal morphology of the ribbon phase, but also an optimal distribution of oxygen vacancies. Our studies thereby provide for the first time compelling experimental evidence correlating the TC with micron to nanoscale inhomogeneity.