Background <p>Surgery of the anterior infratemporal fossa (AITF) and pterygopalatine fossa (PPF) is technically demanding. The Extradural Subtemporal Infratemporal Approach (ESITA) and the Endonasal Endoscopic Transmaxillary Transpterygoid (EEMP) Approach are established routes for accessing these regions. This study quantitatively compares the surgical exposure, surgical freedom, angles of attack, and clinical outcomes achieved with these approaches.</p> Methods <p>ESITA and EEMP were performed on ten sides of five cadaveric heads. Resection volumes were calculated using 3D reconstructions from thin-slice CT scans obtained before and after dissection. Additional measurements—including exposure length, surgical freedom, and angles of attack—were obtained with a neuronavigation system. A retrospective review of twenty-two clinical cases was also conducted to evaluate outcomes.</p> Results <p>ESITA provided a greater resection volume for the AITF than EEMP (92% vs 78.7%, <i>p</i> = 0.043), while EEMP achieved a larger resection volume for the PPF (100% vs 73.1%, <i>p</i> = 0.043). EEMP offered superior vertical exposure to the PPF, whereas both approaches provided comparable AITF exposure. ESITA demonstrated wider surgical freedom and more favorable angles of attack. Clinically, GTR and NTR was achieved in 56% of transcranial, 88% of endoscopic, and 60% of combined cases. Minor complications such as nasal crusting and transient facial numbness occurred mainly in the endoscopic group, while one patient experienced meningitis after transcranial surgery and another developed visual impairment following embolization.</p> Conclusions <p>ESITA is advantageous for AITF lesions, while EEMP is better suited for PPF pathology. ESITA also provides greater surgical maneuverability compared to EEMP.</p>