Topical drug delivery systems offer a targeted and patient-compliant approach for managing psoriasis, enabling noninvasive, localized, and sustained therapy, with reduced systemic side effects and improved therapeutic outcomes. In this study, we prepared phospholipid complex (PLC) based gel of methotrexate (MTX) and erlotinib (ERL) as a potential dual treatment for psoriasis. The phospholipids used in this study were biocompatible and exhibited enhanced skin permeation. The physical interactions between drugs and phospholipids in the MTX-loaded phospholipid complex (MPLC) and ERL-loaded phospholipid complex (EPLC) were characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (H NMR), and powder X-ray diffraction (P-XRD). Scanning electron microscopy (SEM) confirmed amorphization of the drug upon complexation, and transmission electron microscopy (TEM) indicated that the complexes formed a spherical morphology. Furthermore, gel-embedded drug-phospholipid complexes exhibited slower diffusion-based sustained release profiles, with ~ 40% release of ERL from EPLC and ~ 60% release of MTX from MPLC over 24 h, in contrast to the faster release of ~ 65% and ~ 90% observed for free ERL and MTX, respectively. Skin permeation studies (Franz diffusion cells), dermal pharmacokinetics studies, and in vivo antipsoriatic activity studies (imiquimod (IMQ)-induced psoriasis model) were performed to evaluate the efficacy of the optimized formulation. This first-in-class combination therapy provides better lesion control and reduced inflammation while minimizing systemic adverse effects, highlighting the potential of drug-phospholipid complexes for targeted, sustained delivery in psoriasis treatment.