2-Indolinone nucleus is considered one of a promising heterocyclic core in medicinal chemistry that showed numerous range of activity among which antimicrobial, antioxidant, antiviral, antitubercular and anticancer activities. Cancer targeting is still an issue so there is a need for developing new agents that inhibit cancer growth without or low effect on normal body cells. Some derivatives of indolin-2-one are known to be a critical structure in some inhibitors of receptor tyrosine kinases (RTKs); a cancer target therapy, for example, Sunitinib. Herein in this review we focus on 2-indolinone derivatives as RTKs inhibitors as cancer targeting therapy.