Introduction: Melanoma is a global disease that is predominant in Western countries. How-ever, reliable data resources and comprehensive studies on the theragnostic efficiency of miRNAs in melanoma are scarce. Hence, a decisive study or comprehensive review is required to collate the evidence for profiling miRNAs as a theragnostic marker. This protocol details a comprehensive systematic review and meta-analysis on the impact of miRNAs on chemoresistance and their association with theragnosis in melanoma. Methods and analysis: The articles will be retrieved from online bibliographic databases, including Cochrane Review, EMBASE, MEDLINE, PubMed, Scopus, Science Direct, and Web of Science, with different permutations of ‘keywords’. To obtain full-text papers of relevant research, a stated search method will be used, along with selection criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Protocols 2015 (PRISMA-P) standards were used to create this study protocol. The hazard ratio (HR) with a 95% confidence interval will be analyzed using Comprehensive Meta-Analysis (CMA) software 3.0. (CI). The pooled effect size will be calculated using a random or fixed-effects meta-analysis model. Cochran’s Q test and the I2 statistic will be used to determine heterogeneity. Egger’s bias indicator test, Orwin’s and the classic fail-safe N tests, the Begg and Mazumdar rank collection test, and Duval and Tweedie’s trim and fill calculation will all be used to determine publication bias. The overall standard deviation will be evaluated using Z-statistics. Subgroup analyses will be performed according to the melanoma participants’ clinicopathological and biological characteristics and methodological factors if sufficient studies and retrieved data are identified and available. The source of heterogeneity will be assessed using a meta-regression analysis. A pairwise matrix could be developed using either a pairwise correlation or expression associations of miRNA with patients’ survival for the same studies.