In this study, using the density functional theory (DFT) computational methods and Monte Carlo simulation, the interaction of methotrexate (MTX) and its derivative (L-FMTX) with Single-walled carbon nanotubes (SWCNTS) was investigated. Through the DFT method, the effects of different solvents (water, methanol, ethanol, dimethyl sulfoxide and dimethylformamide) on the interaction of methotrexate (MTX) and its derivative (L-FMTX) with Single-walled carbon nanotubes within the Onsager self-consistent reaction field (SCRF) model, as well as the effects of temperature on the stability of interactions between compounds in various solvents were studied. Using theoretical calculations, The effects of temperature on the stability of the bond between the compounds and total density of states (DOS) as well as boundary molecular orbitals (FMOS) related to the mentioned compounds were investigated. The molecular properties of compounds such as ionization potential (I), electron affinity (A), chemical hardness (η), electronic chemical potential (µ) and electronegativity (χ) were also used. The interaction resulting from the binding of methotrexate (MTX) to Single-walled carbon nanotubes as well as the interaction of the methotrexate derivative (L-FMTX) with Single-walled carbon nanotubes were studied through molecular mechanics using the Monte Carlo simulation method in the four AMBER, OPLS, CHARMM and MM+ force fields at different temperatures. The results showed that the MTX structure with the SWCNT single wall nanotube was more stable than the L-FMTX structure with SWCNT single wall nanotube. The results showed that the most stable solvent for the above-mentioned structures was water and that the most efficient force field was MM+. Manuscript profile