Altogether, this collective evidence emphasizes the need to investigate the impact of obesity on pharmacokinetics and efficacy in clinical drug trials, especially given the expansion of the BC therapeutic landscape in the last decade with the emergence of novel selective estrogen receptor degraders (SERDs), CDK4/6 inhibitors, immune checkpoint inhibitors (ICIs), antibody–drug conjugates (ADCs), PI3K and tyrosine-kinase inhibitors, PARP-inhibitors as well as other targeted therapies. The gene discussed is ESR1; the disease is Obesity.