Objective: To summarise the evidence on the use of metagenomic next-generation sequencing to characterise the respiratory microbiome in paediatric patients with cystic fibrosis (CF), with a focus on early-life microbial evolution, development of the airway resistome and the clinical utility of sequencing-based approaches in practice. Introduction: Early-life development of the respiratory microbiome plays a significant role in shaping long-term pulmonary outcomes in children with CF. Conventional culture-based diagnostics lack the sensitivity required to capture the complexity of airway microbial communities. Metagenomic sequencing enables culture-independent identification of pathogens and antimicrobial resistance genes, resulting in an expansion of literature utilising sequencing-based approaches to characterise the CF respiratory microbiome. The clinical significance of early-life microbiome variation and the translational value of these data remain poorly understood. Eligibility Criteria: Inclusion- studies that utilise metagenomic sequencing, including targeted 16S rRNA amplicon sequencing and untargeted shotgun sequencing, to characterise the bacterial respiratory microbiome of children and young people up to their 18th birthday with CF. Exclusion- animal models; in vitro, tissue-based or in silico studies; case-studies <10 participants, editorials, conference abstracts and review studies. Methods: The review will be conducted in accordance with Joanna Briggs Institute and PRISMA-Scoping Review (ScR) methodology. The databases to be searched will include Medline, and Web of Science with an additional for grey literature search via Google and Google Scholar, with no time or language restrictions. Two independent reviewers will screen by title and abstract, then by full-text review. The results of the search, study selection process and reasons for exclusion at full-text review will be reported in the PRISMA-ScR flow diagram. Data will be extracted into a chart. Key study characteristics and findings will be presented and discussed descriptively, supported by tabular summaries; highlighting how the available evidence relates to the review question.