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This paper aims to explore and describe the challenges experienced by nurses caring for persons diagnosed with intellectual disability. Caring for persons with intellectual disability is understood be challenging for families. This could be worse for nurses due to the challenging behaviour the persons with intellectual disability present with. This may be exacerbated by the attitudes nurses have towards persons with intellectual disability. The researchers ask the following questions: “What are the challenges experienced by nurses caring for persons with intellectual disability?” We employed an exploratory-descriptive research design, using in-depth individual face-to-face interviews to explore the nurses’ experiences. Using Tesch’s method of open coding, two overarching themes emerged: (1) Care-related challenges and (2). Facilitation of a supportive, caring environment. The findings of the study demonstrate that the experienced challenges are related to the mental status of the persons diagnosed with intellectual disability, the therapeutic environment, shortage of specialized personnel and role ambiguity. Hence, the nurses yearn for a supportive environment which includes family support and support from the institution's management, including the provision of psychosocial support, which plays a pivotal role in achieving a safe, caring environment. The findings of this study could be used to develop strategies to facilitate a supportive, caring environment to minimize therapeutic challenges.