<p>Space-charge layers (SCLs) at heterogeneous interfaces generate electrostatic potential drops that can enhance or impede ionic and electronic transport near the interface. In solid-state Li-ion batteries, previous models typically only consider Li-ions as the mobile defect, even though cations, anions, and electrons can all participate in SCL formation. Here, we introduce a general first-principles defect-based framework to quantify these multi-species contributions and apply it to LiPON/Li_<i>x</i>V₂O₅ interfaces (<i>x</i> = 0, 1, 2 for the alpha, delta, and gamma phases). A systematic screening of charged point defect formation energies identified Li-ion vacancies, Li-ion interstitials, and O-ion vacancies as dominant species. The model reveals spontaneous Li-ion transfer from LiPON into Li_<i>x</i>V₂O₅ and O-species transfer in the opposite direction, behaviors missed by Li-only treatments. Band alignments across the interfaces show electrons initially transferring from LiPON into V₂O₅, however, when the lithium content increases in Li_<i>x</i>V₂O₅, the direction of electron transfer reverses. Consequently, the predicted band-bending switches from downward bending in V₂O₅ to upward bending in the LiV₂O₅ and Li₂V₂O₅ phases. The implications of these SCL-induced potentials for Li-ion and electron transport are discussed for solid-state batteries and electrochemical neuromorphic devices, highlighting the importance of explicitly accounting for multi-ion defect transfer.</p>