This study provides an in-depth interpretation of the ALTER-L043 phase II randomized trial, focusing on the efficacy and safety of perioperative penpulimab plus anlotinib with or without chemotherapy in resectable non-small cell lung cancer (NSCLC). The investigation was motivated by the need to optimize combination strategies beyond current immunotherapy-chemotherapy regimens, including the potential of "chemotherapy-free" approaches. The analysis encompassed the design, patient characteristics, pathological response rates, and safety profile of the trial, with comparisons to recent phase III studies. Results demonstrated that the triplet regimen achieved a major pathological response rate of 76.0% (19/25), surpassing the doublet regimens [57.7% (15/26) vs. 52.4% (11/21)], with notable benefits in squamous cell carcinoma [79.0% (15/19) vs. 55.0% (11/20) vs. 50.0% (9/18)] and stage ⅢA/ⅢB disease [82.4% (14/17) vs. 55.6% (5/9) vs. 50.0% (6/12)]. The chemotherapy-free doublet also showed promising efficacy. Safety profiles were manageable across groups. In conclusion, penpulimab plus anlotinib-based therapy offers a viable perioperative option, with the triplet regimen potentially suited for high-burden disease and the doublet providing an alternative for chemotherapy-ineligible patients, though phase Ⅲ confirmation is warranted.