Various metal-based electrocatalysts from nanocrystals, to clusters and single-atoms, have been well-discovered towards high-efficient power devices and electrocatalytic conversion. To accelerate energy transformation materials discovery, developing high-throughput DFT calculations and machine-learning techniques is of great necessity. This review comprehensively outlines the latest progress of theory-guided design of advanced energy transformation materials. Especially, we focus on the study of single atoms in various power devices, such as fuel cell (oxygen reduction reaction, ORR; acid oxidation reaction; alcohol oxidation reaction), and other reactions for energy-related electrocatalytic conversion of small molecules, such as H2O2 evolution reactions (2e− ORR), water splitting (H2 evolution reaction/O2 evolution reaction, HER/OER), N2 reduction reaction (NRR), and CO2 reduction reactions (CO2RR). Firstly, the electronic structure, interaction mechanism, and reaction activation path are discussed to provide an overall blueprint in electrocatalysis and batteries mentioned above. Thereafter, the experimental synthesis strategies, structural recognition, and electrocatalytic performance for the advanced energy transformation materials are figured out. Finally, some viewpoints into the current issues and future design concept of the advanced energy transformation materials are provided. Display omitted