Background and aimsTo determine the effect of a multimodal intervention (nutritional behavior change and physical exercise) on quality of life, chemotherapy response rate and tolerance, histopathological level of the tumor, body composition, and biochemical parameters, in patients diagnosed with breast cancer during neoadjuvant chemotherapy treatment, and to compare them with the control group. MethodsAnticipated 80 patients diagnosed with breast cancer aged 18–70 years will be recruited for this randomized, unblinded clinical trial based on a nutritional behavior change and physical exercise in patients during the approximately 6 months in which the patient receives neoadjuvant treatment. Participants will be randomly allocated (1:1) to one of two groups (intervention or control). Primary and secondary outcomes will be assessed before the beginning and after the neoadjuvant treatment (before surgery). The primary outcome is quality of life, whereas secondary outcomes include chemotherapy response rate and tolerance, histopathological level of the tumor and body composition (i.e., visceral adipose tissue activity, bone, lean and fat masses). We will analyze blood parameters (i.e., biochemical, inflammatory, and tumor markers) as exploratory outcomes. ConclusionThis study will address the influence of a practical and viable multimodal intervention (i.e., nutritional behavior change and physical exercise) on breast cancer patients undergoing neoadjuvant chemotherapy. Given the practical viability of the intervention in real-world settings, our study holds promise for significant scientific and clinical implications.