This review explores the emerging role of exosomal long non-coding RNAs (lncRNAs) in cancer biology, highlighting their multifaceted interactions, complex modulation mechanisms, and potential therapeutic applications. Exosomal lncRNAs, carried within extracellular vesicles, play a crucial role in tumor progression by facilitating communication networks between tumor cells and their microenvironment. These vesicles are released by various cell types and can affect recipient cells' functions. The review discusses the dynamic interplay between exosomal lncRNAs and cellular components, including interactions with tumor-stroma, immune modulation, and drug resistance mechanisms. Understanding the regulatory functions of exosomal lncRNAs can lead to the development of novel diagnostic markers and therapeutic targets for cancer. Additionally, the review highlights the potential of RNA-based therapeutics, particularly exosomal lncRNAs, as innovative strategies to combat cancer progression and improve treatment outcomes. The review also emphasizes the advantages of exosomes as therapeutic carriers of lncRNAs for personalized targeted therapy in cancer patients.This review explores the emerging role of exosomal long non-coding RNAs (lncRNAs) in cancer biology, highlighting their multifaceted interactions, complex modulation mechanisms, and potential therapeutic applications. Exosomal lncRNAs, carried within extracellular vesicles, play a crucial role in tumor progression by facilitating communication networks between tumor cells and their microenvironment. These vesicles are released by various cell types and can affect recipient cells' functions. The review discusses the dynamic interplay between exosomal lncRNAs and cellular components, including interactions with tumor-stroma, immune modulation, and drug resistance mechanisms. Understanding the regulatory functions of exosomal lncRNAs can lead to the development of novel diagnostic markers and therapeutic targets for cancer. Additionally, the review highlights the potential of RNA-based therapeutics, particularly exosomal lncRNAs, as innovative strategies to combat cancer progression and improve treatment outcomes. The review also emphasizes the advantages of exosomes as therapeutic carriers of lncRNAs for personalized targeted therapy in cancer patients.