Adrenergic β-blockers are medications that attach to β-adrenergic receptors without causing any activation. Rather, they obstruct the effects of β-adrenergic agonists and are employed in the management of several illnesses, including heart failure, stress, anxiety, angina pectoris, myocardial infarction, hypertension, headaches, migraines, and prostate cancer. In general, β-blockers alleviate symptoms and lower the chance of cardiovascular events. β-adrenergic blocking medications have been extensively employed in the treatment of heart failure because of their capacity to avert the negative effects of stimulation of the sympathetic system on the cardiovascular system and offer patients therapeutic advantages. A meta-analysis was conducted to examine the relationship between the Arg389Gly polymorphism in the β1-adrenergic receptor gene with the risk of heart failure in humans. Using data from approximately 7000 patients and 3000 healthy controls, we conducted a meta-analysis to examine the effects of β adrenergic receptor polymorphisms on heart failure prognosis, response to β-blocker medication, and susceptibility to heart failure. The Gly389 homozygote and allele have been shown to raise the risk of heart failure (HF) in East Asians, while decreasing the risk in White people. Overall, the Arg389 homozygote responded to β-blockers more than the Gly389 carrier, but the reductions in HR were comparable. However, patients with heart failure did not significantly benefit from the Arg389 homozygotes' prognosis. Given that these investigations reveal disparities in the effects of metoprolol and carvedilol on the two unique phenotypic profiles of the two receptors under investigation, in vivo data also point to variations in the drug–gene interaction between these two β-adrenoceptor blockers. Metoprolol has been demonstrated to primarily interact with the ADRB1 Arg389Gly-polymorpism about LVEF, blood pressure, and heart rate responses, while carvedilol has most consistently been demonstrated to interact with the ADRB2 Gln27Glu-polymorphism. It appears that those with heart failure may benefit from genetic testing for the genotype involving Arg389Gly and Gln27Glu before starting β-adrenoceptor blocker treatment. Since this would provide the best possible treatment choice with the three suggested β-adrenoceptor blockers.