These unassisted tandem devices solely driven by sunlight showcase the potential of OPV-based PEC biohybrids as a sustainable approach for the direct synthesis of industrially important platform chemicals. Our system takes advantage of a biocompatible organic photocathode design that maintains its performance even under neutral pH conditions , simultaneously achieving high onset potentials, unprecedented photocurrent densities and near-unity FYs in a benign bicarbonate solution (see literature comparisons in Tables ). The absence of non-innocent buffer components endows greater flexibility in the synthetic application of our biohybrid devices, including the direct coupling to water oxidation. The versatile nature of our PEC biohybrid design also allows for future applications with enzymatic cascades in a one-pot reaction , driving the synthesis of fuels such as methanol or the C-H activation of inert hydrocarbons . Whole cells could also be integrated in the IO-TiO2 matrix and biologically engineered to achieve more complex biochemical transformations. Our computational and spectroscopic methods provide the essential tools to further understand fundamental charge transfer mechanisms and catalytic reaction kinetics in 3-dimensional inverse opal electrodes, which may be extended to other porous structures such as micropillars and reactor designs .