The interaction between itinerant π and localized d electrons in metal-phthalocyanines, namely, Jπd interaction, is considered as responsible for the giant negative magnetoresistance observed in several phthalocyanine-based conductors, among many other important physical properties. Despite the fundamental and technological importance of this on-site intramolecular interaction, its giant ferromagnetic nature has been only recently demonstrated by the experiments conducted by Murakawa et al. in the neutral radical [Fe(Pc)(CN)2]·2CHCl3 ( Phys. Rev. B 2015 , 92 , 054429 ). In this article, we present the theoretical evaluation of this interaction combining wave function-based electronic calculations on isolated Fe(Pc)(CN)2 molecules and density functional theory-based periodic calculations on the crystal. Our calculations confirm the ferromagnetic nature of the π-d interaction, with a coupling constant as large as Jπd/kB = 570 K, in excellent agreement with the experiments, and the presence of intermolecular antiferromagnetic interactions driven by the π-π overlap of neighboring phthalocyaninato molecules. The analysis of the wave function of the ground state of the Fe(Pc)(CN)2 molecule provides the clues of the origin of this giant ferromagnetic π-d interaction.