Respiratory syncytial virus (RSV) is one of the major pathogens frequently associated with severe respiratory tract infections in younger children and older adults globally. There is an unmet need with a lack of routine country-specific databases and/or RSV surveillance systems on RSV disease burden among adults in most low- and middle-income countries, including Cameroon. We aim to estimate the adult RSV burden needed to develop a framework for establishing an RSV surveillance database in Cameroon. A two-phase study approach will be implemented, including a literature review and a review of medical records. First, a systematic review of available literature will provide insights into the current burden of RSV in adults in Cameroon, searching the following databases: Global Health, PubMed, CINAHL, Embase, African Journal Online Library, Scopus, Global Index Medicus, Cochrane databases, and grey literature search. Identified studies will be included if they reported on the RSV burden of disease among Cameroonian adults aged ≥18 years from 1st January 1990 to 31st December 2023. A narrative synthesis of the evidence will be provided. A meta-analysis will be conducted using a random effect model, when feasible. Two co-authors will independently perform data screening, extraction, and synthesis and will be reported according to the PRISMA-P guidelines for writing systematic review protocols. Secondly, a retrospective cohort design will permit data analysis on RSV among adults in the laboratory registers at the National Influenza Center. Medical records will be reviewed to link patients' files from emanating hospitals to capture relevant demographic, laboratory, and clinical data. The International Classification of Diseases and Clinical Modifications 10th revision (ICD-10-CM) codes will be used to classify the different RSV outcomes retrospectively. The primary outcome is quantifying the RSV burden among the adult population, which can help inform policy on establishing an RSV surveillance database in Cameroon. The secondary outcomes include (i) estimates of RSV prevalence among Cameroonian adult age groups, (ii) RSV determinants, and (iii) clinical outcomes, including proportions of RSV-associated morbidity and/or death among age-stratified Cameroonian adults with medically attended acute respiratory tract infections. The evidence generated from the two projects will be used for further engagement with relevant stakeholders, including policymakers, clinicians, and researchers, to develop a framework for systematically establishing an RSV surveillance database in Cameroon. This study proposal has been registered (CRD42023460616) with the University of York Center for Reviews and Dissemination of the International Prospective Register of Systematic Reviews (PROSPERO).