Cancer remains one of the most important health challenges of modern societies, prompting extensive global research efforts aimed at its control and eradication. Although numerous therapeutic strategies have been developed over time to combat cancer, the persistent issue of resistance exhibited by cancer cells—even against conventional chemotherapy—continues to hinder the success of treatment. Many of these therapeutic interventions fail to produce the desired outcomes due to the adaptability and survival mechanisms of malignant cells. To address this challenge, especially over the past twenty years, researchers have focused on designing more advanced and intelligent methods to overcome cancer resistance. A promising strategy that has emerged involves identifying and targeting the specific vulnerabilities or weak points inherent within neoplastic cells for drug development. Exploiting these molecular weaknesses increases the likelihood of effective elimination of cancer cells while reducing their capacity to develop resistance. Targeted cancer therapy generally uses two primary methodologies. The first approach involves the development of specialized drugs that interact directly with specific molecular targets in cancer cells. The second strategy is the precise delivery of these therapeutic agents specifically to tumor cells, thereby minimizing damage to healthy tissues and reducing adverse side effects. The ultimate objective of these research efforts is to advance personalized medicine—tailoring treatment plans to the unique genetic and molecular characteristics of each patient’s cancer. This patient-centered approach signifies a transformative shift in medical science towards individualized care. In this review, by utilizing credible and up-to-date sources, the various therapeutic targets used in targeted cancer treatment will be discussed, along with the rationale behind their selection and the relevant drugs developed from these approaches.