The discovery of novel anticancer agents remains a critical goal in medicinal chemistry, with innovative synthetic methodologies playing a pivotal role in advancing this field. Recent breakthroughs in CH activation reactions, cyclization reactions, multicomponent reactions, cross-coupling reactions, and photo- and electro-catalytic reactions have enabled the efficient synthesis of new molecular scaffolds exhibiting potent biological activities, including anticancer properties. These methodologies have facilitated the functionalization of natural products, the modification of bioactive molecules, and the generation of entirely new compounds, many of which demonstrate strong antitumor activity. This review summarizes the latest synthetic strategies employed over the past five years for discovering anticancer agents, focusing on their influence on drug design. Additionally, the role of new chemical reactions in expanding chemical space and overcoming challenges, such as drug resistance and selectivity, is highlighted, further emphasizing the importance of discovering novel reactions as a key trend in future drug development.