Multitargeting compounds have emerged as a promising strategy in cancer research, addressing the complexity and adaptability of the disease by simultaneously modulating multiple molecular pathways. In contrast to traditional single-target therapies, which often encounter limitations such as resistance and reduced efficacy, multitarget approaches offer improved therapeutic outcomes by minimizing resistance and reducing toxicity. These compounds are designed to disrupt multiple critical oncogenic processes, including tumor proliferation, angiogenesis, and resistance to apoptosis, thereby enhancing tumor sensitivity to treatment while mitigating the development of therapeutic resistance. This chapter explores the rationale behind multitargeting strategies in cancer therapy, providing a comprehensive review of advancements in the design, synthesis, and biological evaluation of small molecule such compounds.