This systematic review and meta-analysis evaluates the effectiveness of neoadjuvant chemoimmunotherapy compared to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC). The study included 43 trials with 5431 patients, focusing on surgical, pathological, and efficacy outcomes. Key findings include: - **Surgical Outcomes**: Neoadjuvant chemoimmunotherapy was associated with a higher rate of surgical resection and R0 resection compared to neoadjuvant chemotherapy. - **Pathological Outcomes**: There was a significant increase in major pathological response (MPR) and complete pathological response (pCR) rates with neoadjuvant chemoimmunotherapy. - **Efficacy Outcomes**: Neoadjuvant chemoimmunotherapy showed improved event-free survival (EFS) and overall survival (OS) compared to neoadjuvant chemotherapy, particularly in patients with PD-L1 levels of 1% or greater. - **Adverse Events**: The rate of serious adverse events (SRAEs) and treatment-related adverse events (TRAEs) was similar between the two groups. The study concludes that neoadjuvant chemoimmunotherapy is superior to neoadjuvant chemotherapy in NSCLC, offering better surgical outcomes and improved efficacy. This finding is particularly significant given the recent restriction by the European Medicines Agency to patients with PD-L1 levels of 1% or greater. Future studies should further assess the benefits of neoadjuvant chemoimmunotherapy in different subgroups and explore the impact of specific immunotherapy types.This systematic review and meta-analysis evaluates the effectiveness of neoadjuvant chemoimmunotherapy compared to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC). The study included 43 trials with 5431 patients, focusing on surgical, pathological, and efficacy outcomes. Key findings include: - **Surgical Outcomes**: Neoadjuvant chemoimmunotherapy was associated with a higher rate of surgical resection and R0 resection compared to neoadjuvant chemotherapy. - **Pathological Outcomes**: There was a significant increase in major pathological response (MPR) and complete pathological response (pCR) rates with neoadjuvant chemoimmunotherapy. - **Efficacy Outcomes**: Neoadjuvant chemoimmunotherapy showed improved event-free survival (EFS) and overall survival (OS) compared to neoadjuvant chemotherapy, particularly in patients with PD-L1 levels of 1% or greater. - **Adverse Events**: The rate of serious adverse events (SRAEs) and treatment-related adverse events (TRAEs) was similar between the two groups. The study concludes that neoadjuvant chemoimmunotherapy is superior to neoadjuvant chemotherapy in NSCLC, offering better surgical outcomes and improved efficacy. This finding is particularly significant given the recent restriction by the European Medicines Agency to patients with PD-L1 levels of 1% or greater. Future studies should further assess the benefits of neoadjuvant chemoimmunotherapy in different subgroups and explore the impact of specific immunotherapy types.