The community of women with metastatic breast cancer (MBC) is growing due to greater disease incidence and treatment advances, with over 30% of women now surviving over 5 years (vs. just 4% in 2000). Managing symptoms to maintain the highest quality of life (QOL) is the major goal of care in the metastatic setting. Thus, research that addresses QOL, prognosis and survivorship in this burgeoning and underserved survivor group is critically needed. BC treatment is associated with adverse body composition changes, specifically gains in adipose tissue and reductions in strength and lean mass (LM). Excess adiposity contributes to inflammation and insulin-resistance, which are theorized to promote tumor progression and loss of LM. Low levels of LM are associated with chemotherapy toxicity, increased symptom burden and compromised survival in women with MBC. Lifestyle interventions with early stage BC survivors result in reduced symptoms, improved biomarkers of BC prognosis and enhanced quality of life (QOL). To date, women with MBC have been largely excluded from these trials. Our pilot work in women with MBC demonstrates they are interested, capable, adherent and benefit from participation in a lifestyle intervention. Our results show clinically meaningful improvements in QOL, increased physical activity and strength. We also find improved trends in biomarkers of prognosis, as well as mitochondrial function for women in the immediate intervention vs. control group. Further, our work shows that inflammation-associated microRNAs are differentially expressed following participation in our pilot trial, providing highly novel potential targets to explain mechanisms by which lifestyle interventions improve QOL for these women. We propose a randomized atttention control trial in women with MBC (n=176) to test the immediate and sustained effects of “Every Day Counts,” a 16-week lifestyle intervention based on current lifestyle recommendations for cancer survivors. This trial is adequately powered to examine changes in: 1) QOL - the primary determinant of care in the metastatic setting and (2) body composition, serum biomarkers of prognosis/survival, and pertinent patient reported outcomes. We will also explore mitochondrial function and novel microRNA signatures associated with inflammatory biomarkers and mitochondrial function. Every Day Counts incorporates critical feedback and experiences from our pilot study with women with MBC. Our robust, multidisciplinary study team applies an innovative, highly integrated physiologic model to examine the mechanistic effects of the intervention on decidedly relevant outcomes of interest. The present study challenges current clinical assumptions regarding the presumed ineffectiveness of lifestyle behaviors in the metastatic setting, providing evidence that may inform a paradigm shift expanding the application and relevance of the nutrition and physical activity guidelines to women with MBC. Importantly, this study will provide clinicians with updated evidence and strategies to help make every day count for women with MBC representing high impact for a currently underserved group of survivors.