Non-small cell lung cancer (NSCLC) is a prevalent and lethal malignancy worldwide, posing significant challenges to patient survival. Recent advancements in the field of oncology have introduced immunotherapy and targeted therapy as primary treatment modalities for NSCLC. However, the emergence of treatment resistance and relapse has impeded their long-term effectiveness. Antibody-drug conjugates (ADCs), a rapidly evolving class of anti-cancer agents, offer a promising solution to this issue by harnessing the specificity of monoclonal antibodies and the cytotoxic potency of drug payloads. ADCs have demonstrated notable potential in targeting both highly expressing and low-expressing malignant cells, with early-phase clinical trials yielding superior survival outcomes in NSCLC patients. This review comprehensively outlines the recent advancements in ADC-based strategies for managing NSCLC, supported by evidence from clinical trials. Additionally, the review delves into the oncogenic mechanisms of various biomarkers and offers insights into strategies for their detection in NSCLC patients. Lastly, a forward-looking perspective is provided to address the challenges associated with the utilization of ADCs in NSCLC therapy.