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Simple Summary: Metabolic (bariatric) surgery (MBS) provides the greatest maximum and sustained weight loss among individuals who are morbidly obese. It is more effective than lifestyle interventions in improving or eliminating type 2 diabetes mellitus (T2DM) and in decreasing cardiovascular (CV) risk. Preclinical studies have been conducted to investigate the mechanisms by which MBS leads to the benefits in T2DM and CV risk. In this review, we describe the emerging evidence that MBS may also impact cancer risk and mortality, and whom may benefit most. We describe the long term involvement and commitment of the National Institutes of Health in obesity research in general and MBS in particular. We outline the need for additional research to understand the mechanism(s) by which MBS may influence cancer, since these mechanism(s) are currently unknown. Metabolic (bariatric) surgery (MBS) is recommended for individuals with a BMI > 40 kg/m2 or those with a BMI 35–40 kg/m2 who have one or more obesity related comorbidities. MBS leads to greater initial and sustained weight loss than nonsurgical weight loss approaches. MBS provides dramatic improvement in metabolic function, associated with a reduction in type 2 diabetes mellitus and cardiovascular risk. While the number of MBS procedures performed in the U.S. and worldwide continues to increase, they are still only performed on one percent of the affected population. MBS also appears to reduce the risk of certain obesity related cancers, although which cancers are favorably impacted vary by study, who benefits most is uncertain, and the mechanism(s) driving this risk reduction are mostly speculative. The goal of this manuscript is to highlight (1) emerging evidence that MBS influences cancer risk, and that the potential benefit appears to vary based on cancer, gender, surgical procedure, and likely other variables; (2) the role of the NIH in MBS research in T2DM and CV risk for many years, and more recently in cancer; and (3) the opportunity for research to understand the mechanism(s) by which MBS influences cancer. There is evidence that women benefit more from MBS than men, that MBS may actually increase the risk of colorectal cancer in both women and men, and there is speculation that the benefit in cancer risk reduction may vary according to which MBS procedure an individual undergoes. Herein, we review what is currently known, the historical role of government, especially the National Institutes of Health (NIH), in driving this research, and provide suggestions that we believe could lead to a better understanding of whether and how MBS impacts cancer risk, which cancers are impacted either favorably or unfavorably, the role of the NIH and other research agencies, and key questions to address that will help us to move the science forward. [ABSTRACT FROM AUTHOR]