This critical review examines the underexplored side effect of chemotherapy on wound healing. Chemotherapy, while effective in treating cancer, can also affect normal cells, particularly those involved in wound healing, such as dermal cells and macrophages. The review highlights that chemotherapy drugs can inhibit cellular metabolism, cell division, and angiogenesis, leading to chronic wounds and impaired healing. It discusses the molecular mechanisms behind these effects, including interference with replication, transcription, translation, and cell signaling. The review also explores the impact of chemotherapy on specific skin conditions, such as inflammatory skin rashes, folliculitis, xerosis cutis, and hand-foot syndrome. Additionally, it addresses the role of chemotherapy in causing peripheral neuropathy, which can further complicate wound healing. The authors suggest that cell-based therapies, such as autologous keratinocyte transplantation, and epigenetic interventions may offer potential solutions to mitigate the side effects of chemotherapy on wound healing. Despite the significance of these complications, there is a lack of dedicated treatments, and further research is needed to improve patients' quality of life and manage nonhealing wounds.This critical review examines the underexplored side effect of chemotherapy on wound healing. Chemotherapy, while effective in treating cancer, can also affect normal cells, particularly those involved in wound healing, such as dermal cells and macrophages. The review highlights that chemotherapy drugs can inhibit cellular metabolism, cell division, and angiogenesis, leading to chronic wounds and impaired healing. It discusses the molecular mechanisms behind these effects, including interference with replication, transcription, translation, and cell signaling. The review also explores the impact of chemotherapy on specific skin conditions, such as inflammatory skin rashes, folliculitis, xerosis cutis, and hand-foot syndrome. Additionally, it addresses the role of chemotherapy in causing peripheral neuropathy, which can further complicate wound healing. The authors suggest that cell-based therapies, such as autologous keratinocyte transplantation, and epigenetic interventions may offer potential solutions to mitigate the side effects of chemotherapy on wound healing. Despite the significance of these complications, there is a lack of dedicated treatments, and further research is needed to improve patients' quality of life and manage nonhealing wounds.