Background <p>Dual diagnosis, defined as the coexistence of mental disorders and substance use disorder (SUD), poses a major challenge to mental health nursing practice in Ghana. Patients with dual diagnosis often need comprehensive, coordinated, and long-term care, yet the lack of standardised nursing guidelines in psychiatric hospitals leads to fragmented service delivery, inconsistent treatment outcomes, and heightened strain on both patients and nursing staff.</p> Aim <p>The aim of this study was to develop and validate guidelines for the nursing care of patients diagnosed with dual diagnosis in psychiatric hospitals of Ghana.</p> Methods <p>An exploratory-descriptive qualitative research design was used to develop and validate the guidelines for the nursing care of patients diagnosed with dual diagnosis in psychiatric hospitals in Ghana. Data were collected through a Comprehensive Literature Review (CLR), individual face-to-face interviews with 23 mental health nurses working in SUD and psychiatric units as well as 16 patients diagnosed with dual diagnosis from the three public psychiatric hospitals in Ghana. From this data, Donabedian model for measuring quality of health care was used to develop guidelines which were validated using Delphi technique.</p> Results <p>Data obtained from the CLR, perceptions of nurses’ on the current nursing care of patients diagnosed with dual diagnosis as well as the patients’ experiences regarding the current nursing care of dual diagnosis were used to develop and validate the guidelines. The study established the central role that nurses play in promoting health and supporting such patients. However, poor infrastructure and inadequate human and material resources, lack of Standardised Operating Procedures (SOPs), lack of consumer involvement in care planning were factors impeding the smooth delivery of nursing care of patients with dual diagnosis in psychiatric hospitals in Ghana.</p> Conclusion <p>The quality of nursing care for patients with dual diagnosis in Ghana is shaped by the interaction between Structure, Process, and Outcome (SPO). Structural gaps such as inadequate training, limited infrastructure, costly treatment, and weak policy support compromise care processes and outcomes. Strengthening structures and optimising processes through therapeutic relationships, strength-based care, effective communication, affordable treatment, and multidisciplinary collaboration could yield positive results. The newly developed standardised, context-specific guidelines are anticipated to enhance care consistency, reduce burden, and promote equitable, effective, and sustainable mental health services for patients with dual diagnosis.</p> Clinical trial <p>Not applicable.</p>