Background: People with profound intellectual disabilities are a population with complex comorbidities. Total pain recognises the interconnectedness of aspects of pain; social, psychological, physical, emotional, spiritual. Pain is under-recognised due to communication challenges and carers perceptions. This review's purpose is to synthesise current literature and provide guidance for future research and care. Methods: Five databases were searched in this mixed methods systematic review (Cinahl, Medline, Psycinfo, Web of Science, Scopus). Articles retrieved were reported via a PRISMA flow diagram. Quality appraisal utilised the mixed methods appraisal tool (MMAT). A convergent qualitative design was the method of data synthesis. Results: Data from 16 included articles generated four themes; Absent voices, reductionist assessment, pain intensity, valuing expertise. Data included physical pain only. Conclusion: Multifaceted pain needs inclusion in research. Assessment must consider the unique expressions of pain by individuals with profound intellectual disabilities. A sharing of expertise may improve pain care.