MicroRNAs (miRNAs) have emerged as crucial regulators of immune system dynamics and cancer progression, positioning them at the forefront of modern immuno-oncology. This chapter explores the multifaceted roles of miRNAs in shaping cancer immunotherapy outcomes, from modulating immune checkpoints and the tumor microenvironment to influencing the efficacy and toxicity of treatment. We examine how specific miRNAs contribute to immunotherapy resistance mechanisms and immune-related adverse events (irAEs), with a focus on their potential as predictive biomarkers. In addition, we highlight therapeutic strategies aimed at restoring or inhibiting miRNA function using novel delivery platforms. Challenges such as off-target effects, biological complexity, and translational barriers are also discussed, alongside emerging technologies that hold promise for overcoming these obstacles. Overall, this chapter underscores the translational value of miRNA biology in advancing precision immunotherapy and improving patient outcomes.