Mental health challenges in the LGBTQ+ community pressing issues as it impact the overall health status. Despite the concerns raised on the discrimination, bias and stereotypes, new challenges arise, implicating challenges to the health sector. The present review of evidence focuses on the resilience factors and the unique mental health challenges faced by members of the LGBTQ+ community. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) were used to identify, select, appraise and synthesize evidence in the present review, whereas the Sample, phenomenon of Interest, Design, Evaluation and Research type (SPIDER) protocol guided the selection of eligible studies to be reviewed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence about the unique mental health challenges and resilience factors within the lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQ+) community. Initial article search was limited to English publications and performed on electronic databases, including Google Scholar, ProQuest, PubMed, and Web of Science. The Cochrane risk of bias assessment tool was used to examine the risk of bias in the individual studies. Risk of bias assessment was performed on the domains, including due to the randomization process, bias due to deviations from intended interventions, bias due to missing outcome data, bias in the measurement of the outcomes, bias in the selection of the reported result, and the overall risk of bias, reflecting the overall risk of bias of the included studies. A qualitative synthesis of results was considered in the present systematic review. The evidence was contrasted and compared against the existing knowledge and theoretical orientation. The present review found that poor dissemination of interventions and implementations are unique mental health challenges among the LGBTQ+ community. The poor implementation and dissemination of interventions substantiate psychological distress, anxiety, depression, and suicidal thoughts and deteriorates quality of life. The web or internet-based implementation of cognitive behavioral therapy emerged as effective resilience factor in the management of mental conditions among members of the LGBTQ+ community. Keywords: LGBTQ+, mental health, treatment, cognitive behavioral therapy, resilience factors, anxiety, depression, and interventions