Epidermal growth factor receptor (EGFR), a transmembrane glycoprotein that mediates cellular signaling pathways involved in cell proliferation, angiogenesis, apoptosis, and metastatic spread, is an important oncogenic drug target. Targeting the intracellular and extracellular domains of the EGFR has been authorized for a number of small-molecule TKIs and mAbs, respectively. However, their clinical application is limited by EGFR catalytic structural domain alterations, cancer heterogeneity, and persistent drug resistance. To bypass these limitations, protease-targeted chimeras (PROTACs) are emerging as an emerging and promising anti-EGFR therapy. PROTACs compensate for the limitations of traditional occupancy-driven small molecules by exploiting intracellular protein destruction processes. Recently, a mushrooming number of heterobifunctional EGFR PROTACs have been created using wild-type (WT) and mutated EGFR TKIs. PROTACs outperformed EGFR TKIs in terms of cellular inhibition, potency, toxicity profiles, and anti-drug resistance. Herein, we present a comprehensive overview of the development of PROTACs targeting EGFR for cancer therapy, while also highlighting the challenges and opportunities associated with the field.