Understanding doping mechanisms is essential for optimizing the doping efficiency and rationally designing next generations of dopants and organic materials. Over the last few years, N-DMBI became a reference solution-processed n-type dopant, affording decent air-stability and record power factor for thermoelectric energy generation. Nevertheless, a complete description of doping mechanism including the activation conditions, the doping pathways, and possible side reactions is still lacking. In this work, we combined experimental and theoretical evidence to clarify the activation conditions of N-DMBI and elucidate the prevalent doping pathway depending on the dielectric constant of the medium. In polar media, direct doping via hydride H− transfer is largely dominant, while, in apolar media, singly occupied molecular orbital-mediated doping after H• release is thermodynamically favored. We show that N-DMBI can be activated not only by thermal annealing above 100 °C, but also by UV-light irradiation at low fluences even in thin films. Our findings stress the importance of working in strictly anoxic environment to avoid parasitic O2-mediated side reactions, even in the presence of a host.