Metallo-organic molecules with highly conjugated pi-electrons, like phthalocyanines (Pc's), are widely investigated for usage in electronic and electro-optic devices. However, their weak coupling with semiconductors is an obstacle to technological applications. Here we report a first-principle theoretical study of some fundamental features of the Pc-semiconductor interaction. Our results shed light on the general problem of organic-inorganic coupling and show that an effective coupling can be achieved by a careful choice of the Pc-substrate system and the semiconductor doping. Our results also reveal a universal alignment of the Pc electronic levels to the semiconductor band gap and suggest a general procedure for designing efficiently coupled organic-inorganic systems.