Transition metal catalysis is crucial for the synthesis of complex molecules, with ligands and bases playing a pivotal role in optimizing cross-coupling reactions. Despite advancements in ligand design and base selection, achieving effective synergy between these components remains challenging. We present here a general approach to nickel-catalyzed photoredox reactions employing tert-butylamine as a cost-effective bifunctional additive, acting as the base and ligand. This method proves effective for C–O and C–N bond-forming reactions with a diverse array of nucleophiles, including phenols, aliphatic alcohols, anilines, sulfonamides, sulfoximines, and imines. Notably, the protocol demonstrates significant applicability in biomolecule derivatization and facilitates sequential one-pot functionalizations. Spectroscopic investigations revealed the robustness of the dynamic catalytic system, while elucidation of structure–reactivity relationships demonstrated how computed molecular properties of both the nucleophile and electrophile correlated to reaction performance, providing a foundation for effective reaction outcome prediction.