Mitochondria are essential organelles involved in energy production, metabolism, and cell proliferation. Mitochondrial DNA (mtDNA) encodes key proteins for the electron transport chain, crucial for oxidative phosphorylation (OXPHOS). Dysregulation of mitochondrial transcription, regulated by mtDNA, POLRMT, TFAM, TFB2M, TEFM, and MTERFs, leads to altered mtDNA expression, metabolic reprogramming, and mitochondrial dysfunction, contributing to cancer progression. Understanding mitochondrial transcription in cancer can aid in diagnosis, prognosis, and treatment. Targeting mitochondrial transcription or related pathways may offer therapeutic strategies. Assessing mitochondrial transcriptional profiles or biomarkers in cancer cells or patient samples may provide diagnostic or prognostic information. Mitochondrial transcription factors, such as TFAM, POLRMT, TFB2M, and MTERFs, are highly expressed in cancer and associated with tumor prognosis. However, their role in cancer is controversial and requires further exploration. Mitochondrial transcription dysregulation is linked to metabolic reorganization in cancer, and the core regulators connecting mitochondrial transcription and nuclear gene expression remain unclear. Differences between mitochondrial transcription dysregulation in cancer cells and cancer stem cells are also not well understood. Targeting mitochondrial transcription in cancer without affecting normal cells is a challenge. Mitochondrial transcription is crucial for mtDNA biogenesis and maintenance, which encode essential components of the OXPHOS system. In cancer cells, alterations in mtDNA and mitochondrial transcription contribute to metabolic rewiring and cancer-related phenotypes. Dysregulation of mitochondrial transcription factors, such as POLRMT, TFAM, TFB2M, and MTERFs, is implicated in cancer development and progression. These factors regulate mitochondrial gene expression and play roles in DNA replication, repair, and mitochondrial function. Alterations in their expression or activity can affect mitochondrial integrity, promote dysfunction, and contribute to tumor initiation and progression. Mitochondrial DNA mutations are common in tumors and are associated with cancer development. mtDNA mutations increase the risk of various cancers, including thyroid carcinoma, breast cancer, lung adenocarcinoma, and acute myeloid leukemia. mtDNA mutations can lead to impaired mitochondrial respiratory chain function and reactive oxygen species (ROS) production, which can induce mutations in genes involved in cell replication, leading to cancer. However, some studies suggest that mtDNA mutations may be "passengers" rather than "drivers" in tumorigenesis. mtDNA can serve as a diagnostic, prognostic biomarker, and therapeutic target. Mutations and copy number changes in mtDNA are common in tumor progression, making mtDNA a potential molecular tool for early tumor detection. mtDNA has unique advantages, including shorter length and higher abundance, making it a sensitive biosensor for detecting rare malignant cells. mtDNA mutations have been found in over 50% of tumors and are associated with tumor occurrence, development, treatment, and prognosis. POLMitochondria are essential organelles involved in energy production, metabolism, and cell proliferation. Mitochondrial DNA (mtDNA) encodes key proteins for the electron transport chain, crucial for oxidative phosphorylation (OXPHOS). Dysregulation of mitochondrial transcription, regulated by mtDNA, POLRMT, TFAM, TFB2M, TEFM, and MTERFs, leads to altered mtDNA expression, metabolic reprogramming, and mitochondrial dysfunction, contributing to cancer progression. Understanding mitochondrial transcription in cancer can aid in diagnosis, prognosis, and treatment. Targeting mitochondrial transcription or related pathways may offer therapeutic strategies. Assessing mitochondrial transcriptional profiles or biomarkers in cancer cells or patient samples may provide diagnostic or prognostic information. Mitochondrial transcription factors, such as TFAM, POLRMT, TFB2M, and MTERFs, are highly expressed in cancer and associated with tumor prognosis. However, their role in cancer is controversial and requires further exploration. Mitochondrial transcription dysregulation is linked to metabolic reorganization in cancer, and the core regulators connecting mitochondrial transcription and nuclear gene expression remain unclear. Differences between mitochondrial transcription dysregulation in cancer cells and cancer stem cells are also not well understood. Targeting mitochondrial transcription in cancer without affecting normal cells is a challenge. Mitochondrial transcription is crucial for mtDNA biogenesis and maintenance, which encode essential components of the OXPHOS system. In cancer cells, alterations in mtDNA and mitochondrial transcription contribute to metabolic rewiring and cancer-related phenotypes. Dysregulation of mitochondrial transcription factors, such as POLRMT, TFAM, TFB2M, and MTERFs, is implicated in cancer development and progression. These factors regulate mitochondrial gene expression and play roles in DNA replication, repair, and mitochondrial function. Alterations in their expression or activity can affect mitochondrial integrity, promote dysfunction, and contribute to tumor initiation and progression. Mitochondrial DNA mutations are common in tumors and are associated with cancer development. mtDNA mutations increase the risk of various cancers, including thyroid carcinoma, breast cancer, lung adenocarcinoma, and acute myeloid leukemia. mtDNA mutations can lead to impaired mitochondrial respiratory chain function and reactive oxygen species (ROS) production, which can induce mutations in genes involved in cell replication, leading to cancer. However, some studies suggest that mtDNA mutations may be "passengers" rather than "drivers" in tumorigenesis. mtDNA can serve as a diagnostic, prognostic biomarker, and therapeutic target. Mutations and copy number changes in mtDNA are common in tumor progression, making mtDNA a potential molecular tool for early tumor detection. mtDNA has unique advantages, including shorter length and higher abundance, making it a sensitive biosensor for detecting rare malignant cells. mtDNA mutations have been found in over 50% of tumors and are associated with tumor occurrence, development, treatment, and prognosis. POL