The article provides an overview of kinase-targeted cancer therapies, highlighting their progress, challenges, and future directions. Protein kinases, which are involved in various cellular processes, have been identified as key players in cancer initiation and progression. The development of small-molecule kinase inhibitors has shown significant success in clinical therapy, with 37 kinase inhibitors receiving FDA approval for treating malignancies such as breast and lung cancer. Additionally, about 150 kinase-targeted drugs are in clinical trials, and many are in preclinical stages. However, factors such as tumor genetics, microenvironment, drug resistance, and pharmacogenomics can affect the efficacy of these molecules. The review discusses the role of kinases in cancer, the development timeline of kinase inhibitors, and the different types of kinase inhibitors, including ATP-competitive, allosteric, substrate-directed, and covalent inhibitors. It also covers the biochemical mechanisms of action and recent clinical developments, emphasizing the importance of precision medicine and natural bioactives as potential kinase inhibitors. Despite advancements, challenges such as drug resistance and the need for more selective inhibitors remain significant.The article provides an overview of kinase-targeted cancer therapies, highlighting their progress, challenges, and future directions. Protein kinases, which are involved in various cellular processes, have been identified as key players in cancer initiation and progression. The development of small-molecule kinase inhibitors has shown significant success in clinical therapy, with 37 kinase inhibitors receiving FDA approval for treating malignancies such as breast and lung cancer. Additionally, about 150 kinase-targeted drugs are in clinical trials, and many are in preclinical stages. However, factors such as tumor genetics, microenvironment, drug resistance, and pharmacogenomics can affect the efficacy of these molecules. The review discusses the role of kinases in cancer, the development timeline of kinase inhibitors, and the different types of kinase inhibitors, including ATP-competitive, allosteric, substrate-directed, and covalent inhibitors. It also covers the biochemical mechanisms of action and recent clinical developments, emphasizing the importance of precision medicine and natural bioactives as potential kinase inhibitors. Despite advancements, challenges such as drug resistance and the need for more selective inhibitors remain significant.