more than 30 years of empirical optimization [1,2] from the first proof of concept by Tang delivering only 1% power conversion efficiency (PCE) in 1986, [3] to develop the latest Y-series of non-fullerene acceptor (NFA) molecules [4,5] that now yield efficiencies close to 20%. [6][7][8][9][10][11] The field of OPV has always been in need of design principles that could guide the synthesis of new molecules. In parallel to molecular engineering, our understanding of the photophysics governing the solar cell performances has considerably increased in the last 30 years, and such sets of meaningful design rules have started to solidify. [12][13][14][15] Furthermore, first principlebased computational materials chemistry has progressed to the point where energy levels can not only be computed in the gas phase, but also extrapolated to films, which allows for screening many potential structures of OPV materials and selecting the most promising for synthesis. [14] For low-bandgap NFA-based solar cells, we previously showed that the acceptor's ionization energy has to be ≈0.45 eV higher (more negative with respect to vacuum) than that of the donor, to maximize exciton quenching by hole transfer from the acceptor to the donor and in turn the solar cells' internal quantum efficiency (IQE). [12,14] We showed that this hole transfer efficiency sets a ceiling to the solar cells' IQE. The 0.45 eV ionization energy offset ΔIE was shown to be required to counterbalance energy level bending (measured as bias potential B) at the donor-acceptor (D/A) interface, which increases the energy of the interfacial charge transfer (CT) and thus impedes the exciton-to-CT-state transition if ΔIE is low. [12,14,16] The interfacial energy level bending is a consequence of the energetic landscape in NFA-based blends, more specifically the interaction of charges with the surrounding molecules' (NFA and donors) intrinsic quadrupole moments. [12,14,15,17,18] On the other hand, the bending facilitates charge separation (CT to free charge conversion) and diffusion from the interface, explaining the observation of barrier-less charge generation in the top-performing OPV systems. [19] Very recently, we reported that the same applies to ternary blends, composed of one donor and two acceptors. [20] Interestingly, the IQE follows the average IE of both acceptors weighted by their blending (weight) ratio. [20] While Molecular engineering of organic semiconductors provides a virtually unlimited number of possible structures, yet only a handful of combinations lead to state-of-the-art efficiencies in photovoltaic applications. Thus, design rules that guide material development are needed. One such design principle is that in a bulk heterojunction consisting of an electron donor and lower bandgap acceptor an offset (ΔIE) of at least 0.45 eV is required between both materials ionization energies to overcome energy level bending at the donor-acceptor interface, in turn maximizing the charge separation yield and the cell's internal quantum efficiency. The present...