Acute kidney injury, a rapid decline in kidney function coupled with physiological and homeostatic perturbations, is an independent risk factor for both short-term and long-term health outcomes. As incidence of acute kidney injury continues to rise globally, the significant clinical and economic challenge of acute kidney injury underscores the need for its prompt recognition and application of novel and germane strategies to reduce its severity and facilitate recovery. Understanding the multifaceted cascade of events engaged in pathogenesis of acute kidney injury is pivotal for the development of effective preventive and therapeutic strategies. To facilitate an in-depth discussion on emerging therapeutic targets, this review will examine the role of macrophages in kidney injury and repair, explore the alterations in mitochondrial biogenesis dynamics induced by acute kidney injury, and provide insights into the molecular mechanisms underlying the contribution of ferroptosis to kidney injury.