ObjectiveSchizophrenia is a chronic condition, of which the diagnosis and management require comprehensive care. The role mental health nurses play in this management cannot be overemphasised. In an effort to give their best, several challenges confront them which need to be sought and addressed. This study aimed to explore the factors that influence the management of schizophrenia by mental health nurses in the Upper East Region.Design and participantsA descriptive phenomenology design was used in this study. Individual in-depth interviews were conducted among 18 purposively sampled mental health nurses using a semistructured interview guide. Audio-recorded interviews were transcribed verbatim and analysed thematically using Colaizzi’s approach.SettingThe study was conducted in five primary and secondary-level health facilities in the Upper East Region of Ghana.FindingsFive themes were deduced from the theoretical framework, which were as follows: individual factors, interpersonal factors, organisational factors, community-level factors, and policy-level factors. At the individual level, factors such as the condition of the patient at presentation, medication side effects, inadequate knowledge, and poor adherence were identified. Interpersonal factors identified were poor communication, lack of mutual respect, and poor communication, while organisational factors such as inadequate staff, inadequate infrastructure and logistics, and unavailability of antipsychotics were reported. Moreover, the study identified community-level factors such as stigma and cultural beliefs, while policy-level factors such as laws regarding suicide, patient rights, and non-inclusion of mental health services into the National Health Insurance Scheme were reported as factors influencing the management of schizophrenia by mental health nurses.ConclusionsAddressing these factors is essential to ensure sustainable improvements and the effective management of schizophrenia. It is imperative to consider these factors when designing interventions and policies to optimise the management of schizophrenia by mental health nurses in Ghana.