Chemotherapy drugs are long being used to treat cancer either as single drug or in combination with other treatment strategies. However, the current problem with treatment is the development of chemo-resistance properties of cancer cells that causes relapses at the later stages of the treatment. It is therefore necessary to design and develop new drugs or modify existing treatment strategies. Cancer cells show abnormal cell growth and adopt metabolic pathways that are different from normal cells. There are also links between metabolic pathways and chemo-resistance development in cancer cells. This indicates the importance of integration of knowledge on the metabolic pathways of cancer cells prior to new drug design and development for cancer treatment. In this review, we discuss the metabolic pathways associated with chemo-resistance development and focus on existing or new drugs targeting these pathways.