Photophysics and photochemistry are basic subjects in the study of light-matter interactions and are ubiquitous in diverse fields such as biology, energy, materials, and environment. A full understanding of mechanistic photophysics and photochemistry underpins many recent advances and applications. This contribution first provides a short discussion on the theoretical calculation methods we have used in relevant studies, then we introduce our latest progress on the mechanistic photophysics and photochemistry of two classes of molecular systems, namely unnatural bases and sunscreens. For unnatural bases, we disclose the intrinsic driving forces for the ultrafast population to reactive triplet states, impacts of the position and degree of chalcogen substitutions, and the effects of complex environments. For sunscreen molecules, we reveal the photoprotection mechanisms that dissipate excess photon energy to the surroundings by ultrafast internal conversion to the ground state. Finally, relevant theoretical challenges and outlooks are discussed.