In the last few years, non-coherent sensitized photon up-conversion (SUC) in multi-component systems has been developed to achieve significantly high quantum yields for various chromophore combinations at low excitation powers, spanning from the ultraviolet (UV) to near infrared (NIR) spectrum. This promising photon energy management technique became indeed suitable for wide applications in lighting technology and especially in photovoltaics, being able to recover the sub-bandgap photons lost by current devices. A full and general description of the SUC photophysics will be presented, with the analysis of the parameter affecting the photon conversion quantum yield and the quantities which define the optimal working range of any SUC system, namely the threshold and saturation excitation intensity. It will be shown how these quantities depend on intrinsic photophysical properties of the moieties involved and on the SUC solid host matrix. The model proposed represents a powerful tool for evaluation of a newly proposed system, and its reliability will be discussed in respect to an optimized system with SUC yield of 0.26 ± 0.02. The results obtained will outline the research guidelines which must be pursued to optimize the SUC efficiency for its perspective technological applications.