MicroRNAs are posttranscriptional regulators of gene expression that influence biological processes, including cell cycle control, apoptosis, and differentiation. In recent years, their role in cancer biology has become increasingly apparent, especially in DNA damage response (DDR), epithelial–mesenchymal transition (EMT), and resistance to cancer therapies. This chapter provides an overview of current knowledge on how miRNAs regulate these three interconnected processes, with a focus on their mechanisms and clinical implications. MiRNAs affect the DNA damage repair machinery by targeting key components involved in homologous recombination (HR) and non-homologous end joining (NHEJ). Dysregulation of these molecules can compromise genomic stability and contribute to tumor progression or resistance to therapy. Moreover, specific microRNAs act as key regulators of epithelial–mesenchymal transition (EMT), a reversible process that enhances the migratory and invasive potential of cancer cells. By targeting transcription factors such as ZEB1, Snail, and Twist, miRNAs can either suppress or promote EMT, depending on their expression levels. Significantly, miRNAs also influence cancer therapy resistance by modulating cell survival pathways, DNA repair mechanisms, and the tumor microenvironment. Both oncomiRs and tumor-suppressor miRNAs are involved in resistance to chemotherapy, radiotherapy, and targeted treatments, underscoring their potential as predictive biomarkers and therapeutic targets. This chapter discusses key miRNA families involved in DDR, EMT, and resistance (e.g., miR-34, miR-200, let-7, and miR-21), elucidates their molecular interactions, and examines their clinical relevance in oncology. The therapeutic modulation of miRNAs—through the use of mimics or inhibitors—offers a promising approach to sensitize tumors to treatment and overcome resistance. Understanding miRNA-driven regulatory networks is therefore essential for the development of innovative, personalized cancer therapies.