Background: Occupational therapy (OT) interventions on activities of daily living (ADL), cognitive functions, and physical function in middle-aged and older people with chronic stroke. Methods: A systematic review search until November 2024 using five generic databases: PubMed/Medline, Web of Science, Scopus, ScienceDirect, and OT seeker. The PRISMA checklist, RoB 2 (Cochrane, London, UK), and GRADEpro (Evidence Prime Inc., Hamilton, CA) tools assessed the evidence’s methodological quality and certainty. The protocol was registered in PROSPERO (code: CRD42024568225). Results: Of 1733 records were identified across the databases, nine studies were analyzed using the PICOS format. The meta-analysis revealed significant improvements in independent performance of activities of daily living (ADL), as measured by the Canadian Occupational Performance Measure (COPM), in favor of the experimental groups (p = 0.03). No significant differences were found for the other variables analyzed. Conclusions: Performance on ADLs improved significantly according to the COPM, whereas no significant improvements in cognitive or physical function were observed among middle-aged and older chronic stroke survivors. Individual studies highlight the potential benefits of OT interventions that combine cognitive, motor, and technological approaches, such as virtual reality and brain stimulation.