The review discusses the challenges and potential of microRNA (miRNA) therapeutics in cancer treatment. miRNAs are small non-coding RNA molecules that regulate gene expression and are involved in various diseases, including cancers. Despite significant research and investment, miRNA-based therapies remain in early stages, with few entering clinical trials and none approved by the FDA. Key challenges include ensuring miRNA specificity, minimizing off-target effects, and developing effective delivery methods. The review highlights the potential of miRNAs as therapeutic agents but also notes the risks of toxicity and immune responses. Examples of miRNA-based therapies in clinical trials, such as Miravirsen and MRX34, are discussed, along with their successes and failures. The review also explores the role of miRNAs in cancer progression and the development of miRNA-based drugs, including mimics and inhibitors. Additionally, it discusses small-molecule modulators that can influence miRNA expression and the challenges in delivering miRNA therapeutics to specific cells. The review concludes that while miRNAs show promise, significant research is needed to overcome the challenges and realize their therapeutic potential.The review discusses the challenges and potential of microRNA (miRNA) therapeutics in cancer treatment. miRNAs are small non-coding RNA molecules that regulate gene expression and are involved in various diseases, including cancers. Despite significant research and investment, miRNA-based therapies remain in early stages, with few entering clinical trials and none approved by the FDA. Key challenges include ensuring miRNA specificity, minimizing off-target effects, and developing effective delivery methods. The review highlights the potential of miRNAs as therapeutic agents but also notes the risks of toxicity and immune responses. Examples of miRNA-based therapies in clinical trials, such as Miravirsen and MRX34, are discussed, along with their successes and failures. The review also explores the role of miRNAs in cancer progression and the development of miRNA-based drugs, including mimics and inhibitors. Additionally, it discusses small-molecule modulators that can influence miRNA expression and the challenges in delivering miRNA therapeutics to specific cells. The review concludes that while miRNAs show promise, significant research is needed to overcome the challenges and realize their therapeutic potential.