Kinase inhibitors (KIs) represent a popular class of therapeutic agents and chemical probes but most of them tend to be polypharmacological. Receptor and non-receptor Tyrosine KIs can target more than 100 kinases simultaneously compare to other KIs. We here analyze the molecular targets of 41 U.S. Food and Drug Administration (FDA)-approved KIs. We chose 18 drugs (Tyrosine KIs) and sought out to evaluate their selectivity profile and engagement with a number of targets in vivo at clinically relevant doses. We also wanted to see whether there prevails any correlation between the target engagement profile and the reported side effects for specific KIs chosen as test cases. To explore all clinical targets of the 18 KIs, we considered the free (unbound) maximum serum concentration (C-max) of each KI and only chose targets for which the cognate affinities lie within the reported free C-max values, thereby allowing plausible interaction in clinical doses. We retrieved the side effects of those KIs that is reported in the FDA adverse event reporting system. We illustrate how correlation analysis of target-side effect can give a new insight into the off target of KIs and their effect on increasing the toxicity of KIs. These analyses could aid our understanding of the structural-activity relationship of KIs.