Recent preclinical and clinical data accumulate evidence indicating that obesity may worsen the incidence, severity, and mortality of many types of cancer, including breast cancer. In the present review, we discuss the candidate players in this dangerous relationship, namely adipose tissue-related chronic inflammation, immune cell dysregulation, angiogenesis, extracellular matrix stiffness, and genomic instability. Finally, we review some novel therapeutic approaches currently under investigation to prevent and blunt the effects of obesity in breast cancer development and progression, namely caloric restriction, immune checkpoint inhibition, browning of white adipose tissue, and modulation of the microbiota and the immune cell metabolism.