Neoadjuvant chemoimmunotherapy and epidermal growth factor receptor–tyrosine kinase inhibitor are associated with excellent outcomes for patients with early-stage and resectable non–small cell lung cancer. Although they demonstrate increased pathologic response rates, there are also implications for surgical management owing to tissues changes resulting from therapy. With the anticipated increase in uptake of these treatment strategies, it is critical for surgeons to identify potential challenges, especially as clinical trial data transition to the real-world setting.