Persons with complex care needs that arise due to chronic health conditions, serious illness, or social vulnerability are at increased risk of adverse health outcomes during transitions in care. To inform the development of a best practice guideline, a systematic review was conducted to examine the effect that navigation support has during transitions in care on quality of life, emergency department visits, follow-up visits, patient satisfaction, and readmission rates for persons with complex care needs. Eight databases were searched from 2016 to 2023. Studies were appraised using validated tools and data were extracted and presented narratively. The GRADE approach was used to assess the certainty of the evidence. Seventeen studies were included and the majority focused on transitions from hospital to home. Navigation support was provided for one month to one year following a transition. Results weakly indicate that providing navigation support during transitions in care may increase follow-up visits, reduce readmissions within 30 days, and increase patient satisfaction for persons with complex care needs. There were no important differences for quality of life and emergency department visits within 30 days of a transition. The certainty of the evidence was very low. Providing navigation support during transitions in care may improve outcomes for persons with complex needs; however, there remains uncertainty regarding the effectiveness of this intervention and more high-quality research is needed.