Microbial CO2 upgrading featured with mild operating condition and low energy consumption is one of the preferred choices with the goal of carbon-neutral economy. Some innovative biotechnology platforms based on those microorganisms having characteristic of taking up extracellular electrons are being developed to accomplish the CO2-to-chemical/fuel conversion, especially microbial electrosynthesis (MES) and artificial photosynthetic biohybrid system (PBS). The MES wherein microbial catalysts are capable of converting CO2 into value-added biochemicals and biofuels by directly utilizing an electrode (cathode) as the sole electron donor with high energy efficiency has attracted widespread attention since its inception 10 years ago. Despite substantial progress in bench scale, such technology is still not economically competitive enough for industrialization on account of its low-value products and poor productivity. Nevertheless, the rational construction of electrodes and genetic engineering of producing strains promise to solve these bottlenecks, which will be discussed adequately in this chapter. Furthermore, the PBS that couples microbial cell factories with inorganic nanomaterials capable of light harvesting has also been invented as an up-and-coming alternative to direct solar-to-chemical conversion beyond natural photosynthesis. Although still in the conceptual stage, evidence shows that the PBS achieves higher overall energy efficiency than natural photosynthesis of plants and crops for CO2-fixation, which is also discussed. The microbial feature of extracellular electron uptake from either renewable electricity or photoelectrons brings many promising possibilities to the CO2 bio-upgrading technologies, while the development of high-performance components and coordinated optimization of reaction systems are necessary for these technologies to move from the laboratory to the industrialization.