The purpose of this review is to identify and synthesize existing evidence on the effectiveness of self-care interventions, conducted autonomously or with the support of nursing professionals, in promoting the health and well-being of adults aged 45–64. Globally, self-care and nursing care are essential components of healthcare systems, particularly in health promotion throughout the lifespan. Self-care, defined as a set of practices performed by individuals with or without healthcare professional support, plays a critical role in preventing diseases and maintaining well-being. This review focuses on adults aged 45–64, a group facing specific health management challenges, requiring interventions that enhance health and prevent long-term complications. Studies evaluating self-care strategies, nursing interventions, and/or care planning targeting health promotion in adults (45–64 years) will be included without language restrictions. Interventions may involve health education, behavioral change programs, technological support, or community-based approaches. The systematic review will search databases such as EBSCOhost, CINAHL Ultimate, MEDLINE Ultimate, PubMed, MedicLatina, Psychology and Behavioral Sciences Collection, and Academic Search Complete. Two independent reviewers will screen titles, abstracts, and keywords. Full-text evaluations will follow for eligible studies, with disagreements resolved by a third reviewer. Outcomes will measure the interventions’ impact on health status, self-efficacy, quality of life, and adoption of healthy behaviors.