<p>Pharmaceutical contaminations pose serious threats to water quality and human health, while photocatalysis technology provides a solution to the decontamination. However, limited light energy transformation and severe charge recombination hamper the application of photocatalysts for broad-spectrum removal of trace pharmaceuticals. Here, the C − C bond as connection junction served to trigger the versatile synthesis of core-shell MOF@COFs with superior charge separation capability than corresponding parent COFs and MOFs, including MIL@V-TZ, MIL@DaV-TZ, and MIL@DaV-TAPB. The C − C bridge induced lower exciton binding energy (E_b, 42.66 meV) and overlap integral of electron-hole distribution (Sr, 0.57), endowing MIL@V-TZ with photocatalytic efficiencies of 9.8 − 70.2 min⁻¹·g⁻¹ for tetracycline, diclofenac, acetaminophen, and difloxacin. Based on the in-situ grown MIL@V-TZ film, a flow-through system was constructed to achieve ultra-efficient (&gt;99%) and sustainable (up to 6000 min) pharmaceuticals removal without sacrificial agents. In-situ experiments revealed that the electrons were rapidly transferred and highly utilized to form •O₂⁻, dominating the degradation of pharmaceuticals with reduced toxicity. By unveiling the role of C − C bridge in controllable assembly of heterostructures and boosting electron transfer, this work presents an avenue for water decontamination.</p>