OBJECTIVE The mechanisms driving the associations between body weight and physical activity levels and multiple types of cancer are not yet well understood. The purpose of this review was to examine the effects of lifestyle interventions on proposed biomarkers of lifestyle and cancer risk at the level of adipose tissue in humans. METHODS Embase, MEDLINE, and CINAHL were searched by using keywords relating to exercise or diet interventions, adipose tissue biology, and outcomes of interest. Eligible studies included randomized clinical trials of exercise and/or dietary interventions in humans compared with control or other interventions, reporting the collection of subcutaneous abdominal adipose tissue. RESULTS Nineteen studies met criteria for inclusion. Eight studies modified dietary intake, five altered exercise levels, and six studies used a combination of both. Change in subcutaneous adipose tissue gene expression was most commonly observed with dietary weight loss, with a pattern of decrease in leptin, tumor necrosis factor alpha, and interleukin 6, along with an increase in adiponectin. There was limited change with exercise-only interventions or study arms. CONCLUSIONS Interventions leading to weight loss result in an altered gene expression of adipokines and inflammatory markers in subcutaneous adipose tissue, while less change in gene expression was noted with exercise alone.