Cancer has been a significant healthcare concern globally and is severely affecting various populations across continents with 18.1 million new cases and over 9 million deaths in 2018 alone. Several therapeutic approaches have been developed against various cancers like radiation therapy and cytotoxic chemotherapy to eliminate the tumor by physical/chemical-mediated damage to rapidly dividing tumor cells. To some extent, standard cytotoxic therapies have been successful in treating the disease, but they exhibit severe side effects and pose a threat to other fast-growing noncancerous cells. The risks associated with cytotoxic chemotherapy like obliteration of normal rapidly growing cells, induced cytotoxicity, and development of resistance led to the initiation of efforts to discover novel and effective alternate targeted treatment modalities. Pragmatic research endeavours have led to the development of a new area of treatment strategies termed ‘targeted therapies. This approach targets the molecular mechanism of tumor progression and rationally inhibits the abnormal expression of involved genes or pathways, exhibits less toxicity, and shows more efficiency as compared to the traditional treatment regime. This current chapter comprehensively outlines the requirement and role of targeted molecular therapies in cancer, their types, mode of action limitations and future scope. It will aid readers to understand the necessity of alternative treatment modalities in cancer, their effectiveness in contrast to traditional treatment approaches and the combinatorial effect of both the regimes upon requirement. The chapter also sketches the challenges and limitation of this approach and how researchers can overcome them to develop novel, precise and more competent targeted molecular therapies.