Mitochondria, often referred to as the powerhouses of the cell, have emerged as promising targets for cancer therapy due to their pivotal roles in cell survival, apoptosis, and energy metabolism. This sojourn emphasizes the significance of mitochondria-targeted drug delivery systems in cancer therapeutics. The unique characteristics of cancer cell mitochondria, such as altered membrane potential and distinct lipid composition, offer an avenue for selective drug targeting. Several strategies have been explored to exploit these features, including the use of lipophilic cations, mitochondria-penetrating peptides, and nanocarriers tailored for mitochondrial delivery. Mitochondria-targeted drug delivery systems have demonstrated enhanced therapeutic efficacy and reduced systemic toxicity in preclinical models. Some of these systems have made a successful transition to clinical trials, illustrating their potential in real-world oncology settings. However, there remain challenges like intracellular barriers, potential off-target effects, and the complexity of tumor heterogeneity that must be addressed to fully harness the potential of mitochondria-targeted drug delivery systems. As research progresses, it is anticipated that innovative approaches and technologies will be developed to improve the specificity and efficacy of mitochondrial targeting, paving the way for more effective and safer cancer treatments in the future. This review serves as a comprehensive guide to the current state of mitochondria-targeted drug delivery systems for cancer, highlighting key strategies, clinical progress, and prospective avenues for future research.