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Colorectal cancer (CRC) screening disparities and opioid overdose (OD) deaths continue to pose significant public health challenges in Metro Detroit, particularly affecting African American and Middle Eastern North African (MENA) communities. The B.R.I.D.G.E. (Building Relationships to Impact Disparities and Generate Equity) initiative, a nurse-led, multimodal quality improvement (QI) program, demonstrates the vital role of nursing leadership in tackling these 2 pressing epidemics through community-focused, equity-driven strategies. Utilizing the Mobilizing for Action through Planning and Partnerships (MAPP) 2.0 framework, B.R.I.D.G.E. implements targeted interventions across clinical and community settings. These initiatives include enhancing CRC screening through clinic-based QI projects, educating providers, offering transportation assistance, and expanding OD prevention via Narcan administration training, Screening, Brief Intervention, Referral to Treatment (SBIRT), and Mental Health First Aid (MHFA). By empowering nurses as trusted community advocates and cultivating strong cross-sector partnerships, B.R.I.D.G.E. effectively improves care delivery, advances health equity, and nurtures sustainable community engagement. This case study illustrates how nurse-led interventions can dismantle structural barriers, enhance health outcomes, and serve as scalable models for addressing health disparities in marginalized populations. Utilizing the Mobilizing for Action through Planning and Partnerships (MAPP) 2.0 framework, B.R.I.D.G.E. implements targeted interventions across clinical and community settings. These initiatives include enhancing CRC screening through clinic-based QI projects, educating providers, offering transportation assistance, and expanding OD prevention via Narcan administration training, Screening, Brief Intervention, Referral to Treatment (SBIRT), and Mental Health First Aid (MHFA). By empowering nurses as trusted community advocates and cultivating strong cross-sector partnerships, B.R.I.D.G.E. effectively improves care delivery, advances health equity, and nurtures sustainable community engagement. This case study illustrates how nurse-led interventions can dismantle structural barriers, enhance health outcomes, and serve as scalable models for addressing health disparities in marginalized populations.