Optical manipulation of micro/nanoscale objects is of importance in life sciences, colloidal science, and nanotechnology. Optothermal tweezers exhibit superior manipulation capability at low optical intensity. However, our implicit understanding of the working mechanism has limited the further applications and innovations of optothermal tweezers. Herein, we present an atomistic view of opto-thermo-electro-mechanic coupling in optothermal tweezers, which enables us to rationally design the tweezers for optimum performance in targeted applications. Specifically, we have revealed that the non-uniform temperature distribution induces water polarization and charge separation, which creates the thermoelectric field dominating the optothermal trapping. We further design experiments to systematically verify our atomistic simulations. Guided by our new model, we develop new types of optothermal tweezers of high performance using low-concentrated electrolytes. Moreover, we demonstrate the use of new tweezers in opto-thermophoretic separation of colloidal particles of the same size based on the difference in their surface charge, which has been challenging for conventional optical tweezers. With the atomistic understanding that enables the performance optimization and function expansion, optothermal tweezers will further their impacts.