As an endocrine disruptor, tyrosine kinase inhibitor, and DNA methyltransferase inhibitor, genistein can interfere with breast cancer development. However, as the results of numerous studies are contradictory, it is unclear whether genistein plays a positive or negative role. Retrospective epidemiological studies have indicated that high genistein intake is related to reduced breast cancer risk, but this protective effect has not been reported in clinical trials. Additionally, rodent and cellular studies show that genistein promoted breast cancer progression. Obviously, genistein's bioactivities do not solely depend upon the dose, and simply discussing the overall effects of genistein without considering individual factors is unrealistic. The purpose of this review was to collect relevant studies (over 164) on genistein and breast cancer that were published on PubMed from 1984 to 2019 and to summarize the impact of key individual factors on the bioactivities of genistein in breast cancer prevention and treatment. Furthermore, the related potential molecular mechanisms were explored to explain the contradictions in genistein-breast cancer studies. Our results showed that the intake mode and metabolic characteristics of genistein, as well as the menopausal status, estrogen receptor expression pattern, and gene mutations of the patient, are important factors that should be included when discussing the bioactivities of genistein. A better understanding of the influence of individual factors may enable the precise prediction of personalized responses to dietary genistein exposure. Given that the current information on genistein is mostly restricted to the cellular level, more comprehensive human studies should be performed to clarify the relationship between genistein and breast cancer.