Activating metal–organic frameworks (MOFs) to create open coordination sites is crucial for exploiting the functions of MOFs. This study successfully demonstrates the direct activation of Cu-BTC crystals using rapid and efficient heat treatment assisted by a nanosecond pulse laser. Localized thermal energy was irradiated to the surfaces of the MOFs through a photothermal process, which rapidly and effectively removed solvent residues within the structures of the MOFs. The Cu-BTC crystals synthesized through the solvothermal method were activated through a photothermal process, without inducing any structural damage, by irradiating with the second harmonic of a Nd3+:Y3Al5O12 laser with a wavelength of 355 nm. This process occurred most efficiently without any structural collapse at 30 mJ/cm2, and the residues within the MOFs were removed through the photothermal process within approximately 5 min. Thus, the study offers a novel design strategy involving the rapid activation of MOFs.