Advancing CO₂ Upgrading to Multicarbon Products: Synergies Between Photo/Electrochemical and Biological Conversion

While photo- and electrochemical CO₂ reduction efficiently generate C₁–C₂ molecules (e.g., formate, carbon monoxide, methane, ethylene), their limited selectivity and kinetic constraints impede direct C₂₊ synthesis. Conversely, biological CO₂ fixation excels at producing multicarbon compounds (e.g., glucose, fatty acids, biopolymers) but requires energy-intensive substrates. This Review explores the transformative potential of hybrid abiotic–biotic systems, where tailored C₁–C₂ electron mediators synergize inorganic catalysis with biological conversion to enable scalable C₂₊ production. We critically evaluate: i) recent breakthroughs in photo/electrocatalyst design, reactor engineering, and mechanistic control of C₁–C₂ production; ii) engineered microbial and enzymatic pathways (autotrophic, mixotrophic, and synthetic) that optimize carbon flux toward C₂₊ targets; and iii) integrated system architectures (in situ and spatially segregated), emphasizing mediator biocompatibility, mass-transfer kinetics, and reactor scalability. A focused analysis highlights paired anodic processes (e.g., biomass oxidation) as energy-efficient alternatives to the oxygen evolution reaction. Techno-economic and life-cycle assessments identify key bottlenecks, including mediator toxicity, system integration, and anodic byproduct valorization. By synthesizing interdisciplinary progress, this work identifies pathways to advance C₂₊ production and establishes a roadmap for next-generation CO₂ upgrading technologies.