Purpose of Review <p>This article outlines the role of mitochondrial dynamics in healthy cells and elaborates on how blood cancer cells hijack these processes to support uncontrolled proliferation, stemness, and drug resistance. A comprehensive understanding of the mechanistic details of mitochondrial behavior in malignant hematopoiesis will provide new therapeutic avenues and improve the prediction of therapy responses.</p> Recent Findings <p>Mitochondrial dynamics, governed by the complementary events of fusion and fission, is a key cellular process for maintaining metabolic flexibility, organelle integrity, and cellular homeostasis. Impairment of the dynamic fusion-fission balance can lead to various chronic pathologies. Recent research has highlighted how blood cancer cells exploit mitochondrial remodeling to maintain metabolic efficiency and adjust organellar quality control mechanisms to sustain survival pathways and enable cancer progression. Furthermore, leukemia and lymphoma cells use mitochondrial plasticity to adapt under stress conditions and to evade cell death induced by various clinically used or tested therapeutic regimens. Investigations using blood cancer cell lines, patient-derived samples, and xenograft models have begun to uncover the specific roles and regulatory mechanisms of mitochondrial dynamics proteins in different subtypes of hematologic malignancies, as well as in therapy resistance. Additionally, preclinical studies suggest that targeting these regulators may present novel therapeutic opportunities and serve as predictive biomarkers in blood cancers.</p> Summary <p>This review highlights the therapeutic potential of modulating mitochondrial dynamics, underscoring the need for further integrative studies to fully harness this vulnerability in hematologic malignancies.</p>