MicroRNAs (miRNAs) play a pivotal role in cancer pathogenesis, acting as oncogenes or tumor suppressors depending on their targets and cellular context. Oncogenic miRNAs, or oncomiRs, promote cancer by inhibiting tumor suppressor genes, while tumor suppressor miRNAs inhibit oncogenes. This dual functionality presents challenges and opportunities for therapeutic intervention. Recent advances highlight miRNAs’ potential as therapeutic targets. Targeting oncomiRs with inhibitors can suppress tumor growth and enhance chemotherapy sensitivity. Conversely, mimicking tumor suppressor miRNAs can restore normal gene expression patterns, inhibiting cancer progression. For instance, miR-10b is an oncomiRs in glioblastoma, and its inhibition reduces cancer cell proliferation and invasion. Similarly, miR-21 is associated with therapy resistance in ovarian cancer, and its downregulation can induce apoptosis and reverse drug resistance. The therapeutic potential of miRNA is enhanced by its role in modulating the tumor microenvironment and immune response. For example, miR-155 can sensitize cancer cells to radiation therapy by suppressing the DNA repair mechanism. However, the complex interactions between miRNAs and other cellular components necessitate a holistic approach to miRNA-based therapies. This includes using immunocompetent mouse models and systems biology to fully understand miRNA networks and their implications for cancer treatment. In conclusion, targeting oncogenic miRNAs offers a promising therapeutic strategy for cancer management. By understanding miRNAs’ multifaceted roles and developing effective delivery systems, researchers can harness their potential to improve treatment outcomes and patient survival. Future studies should focus on integrating miRNA therapies with existing treatments to maximize their therapeutic benefits.