Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of gene expression through diverse mechanisms, including regulation of protein localization, sequestration of miRNAs, recruitment of chromatin modifiers, and modulation of signaling pathways. Accumulating evidence highlights their pivotal roles in tumor initiation, progression, and the development of therapeutic resistance. In this review, we comprehensively summarized the existing literature to identify lncRNAs associated with treatment responses in non-small cell lung cancer (NSCLC). Specifically, we categorized these lncRNAs based on their mechanisms of action in mediating resistance to chemotherapy, targeted therapy, and radiotherapy. Our analysis revealed that aberrant expression of various lncRNAs contributes to the development, metastasis, and therapeutic resistance in NSCLC, ultimately leading to poor clinical outcomes. By elucidating the intricate mechanisms through which lncRNAs modulate therapeutic responses, this review aims to provide mechanistic insights into the heterogeneous treatment outcomes observed in NSCLC patients and unveil potential therapeutic targets for overcoming drug resistance.