Obesity has been known to be a major risk factor for various types of cancers for several decades. More recently, the relationship between dysregulated adipokines and cancer development has been the focus of much research. Adipose tissue is an important endocrine organ that secretes adipokines that affect both autocrine and paracrine signaling. These adipokines modulate inflammation, induce insulin resistance, and regulate their own behavior and production. Adipokine-production dysregulation is due to physiological changes in adipose tissue that prompt molecular modifications, including low-grade inflammation and the stimulatory production of reactive oxygen species. Additionally, studies have linked DNA damage response, genomic instability, and the innate immune response to tumorigenesis. Further investigation of adipokines and their role in the promotion of genomic instability may clarify the link between obesity and cancer, as well as elucidate potential pharmaceutical targets. In this review, we discuss the progress of recent literature, focusing on the impact of adipokines, genomic instability, and the innate immune response on increasing the risk of cancer.