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Mitochondrial dynamics have pillar roles in several diseases including cancer. Cancer cell survival is monitored by mitochondria which impacts several cellular functions such as cell metabolism, calcium signaling, and reactive oxygen species (ROS) production. The equilibrium of death and survival rate of mitochondria is important for healthy cellular processes. Whereas inhibition of mitochondrial metabolism and dynamics can have crucial regulatory decision between cell survival and death. The steady rate of physiological flux of both mitochondrial fission and fusion is strongly related to the preservation of cellular bioenergetics. Dysregulation of mitochondrial dynamics including fission and fusion is a critical machinery in cell accompanied with crosstalk in cancer progression and resistance. Many cancer cells express high levels of Dynamin-related protein 1 (Drpl) to induce cancer cell invasion, metastasis and chemoresistance including breast cancer, liver cancer, pancreatic cancer, and colon cancer. Targeting Drpl by inhibitors such as Midivi-1 helps to enhance the responsiveness of cancer cells towards chemotherapy. The review showed Drp-1 linked processes such as mitochondrial dynamics and relationship with cancer, invasion and chemoresistance along with computational assessing of all publicly available Drp-1 inhibitors-Drpl-IN-1, Dynole 34-2, Trimethyloctadecyl-ammonium bromide, and Schaftoside showed potential inhibitory effect on Drp-1 as compared to standard Mdivi-1. This emerging approach may have extensive strength in the context of cancer development and chemoresistance and further work is needed to aid in more effective cancer management. [ABSTRACT FROM AUTHOR]