Kinase inhibitors and kinase-targeted cancer therapies have seen significant advancements, with over 120 small-molecule kinase inhibitors (SMKIs) approved globally, including 70 FDA-approved drugs for cancer treatment. These inhibitors target various kinases, such as the epidermal growth factor receptor (EGFR) family, and include monoclonal antibodies, nanobodies, peptides, and novel approaches like kinase degraders and protein kinase interaction inhibitors. Despite their potential, challenges such as drug resistance and toxicity when combined with immunotherapy remain. The tyrosine kinase family has 70% of its targets in various stages of development, while 30% remain underexplored. Computational technologies are accelerating the development of new inhibitors and repurposing existing drugs. Recent FDA-approved SMKIs highlight the importance of blood-brain barrier permeability for long-term patient benefits. This review summarizes recent FDA-approved SMKIs, explores emerging inhibition strategies, and addresses current challenges and future directions. Kinase inhibitors continue to face hurdles, including acquired resistance and off-target effects. New strategies, such as covalent inhibitors and allosteric inhibitors, show promise in overcoming resistance. The development of kinase inhibitors remains highly promising, with ongoing research into novel targets and improved selectivity. The review also discusses the classification of SMKIs based on their mechanism of action and binding sites, highlighting the importance of targeting specific kinases and mutations. The role of computational technologies in accelerating inhibitor development is emphasized. The review concludes with a focus on the potential of kinase inhibitors in overcoming resistance and improving cancer treatment outcomes.Kinase inhibitors and kinase-targeted cancer therapies have seen significant advancements, with over 120 small-molecule kinase inhibitors (SMKIs) approved globally, including 70 FDA-approved drugs for cancer treatment. These inhibitors target various kinases, such as the epidermal growth factor receptor (EGFR) family, and include monoclonal antibodies, nanobodies, peptides, and novel approaches like kinase degraders and protein kinase interaction inhibitors. Despite their potential, challenges such as drug resistance and toxicity when combined with immunotherapy remain. The tyrosine kinase family has 70% of its targets in various stages of development, while 30% remain underexplored. Computational technologies are accelerating the development of new inhibitors and repurposing existing drugs. Recent FDA-approved SMKIs highlight the importance of blood-brain barrier permeability for long-term patient benefits. This review summarizes recent FDA-approved SMKIs, explores emerging inhibition strategies, and addresses current challenges and future directions. Kinase inhibitors continue to face hurdles, including acquired resistance and off-target effects. New strategies, such as covalent inhibitors and allosteric inhibitors, show promise in overcoming resistance. The development of kinase inhibitors remains highly promising, with ongoing research into novel targets and improved selectivity. The review also discusses the classification of SMKIs based on their mechanism of action and binding sites, highlighting the importance of targeting specific kinases and mutations. The role of computational technologies in accelerating inhibitor development is emphasized. The review concludes with a focus on the potential of kinase inhibitors in overcoming resistance and improving cancer treatment outcomes.