Advanced and metastatic RET-driven solid cancer is not susceptible to chemotherapy or radiotherapy. The development of targeted therapy has led to a new therapeutic model. Nevertheless, no systematic evaluation of their efficacy and safety has been carried out in RET-driven solid cancer. Systematic review and single-arm meta-analysis were performed. Four electronic databases were searched (PubMed, Embase, Cochrane Library, and Web of Science) from each database’s inception date until February 27, 2022. Study inclusion criteria focused on peer-reviewed published articles that reported the efficacy and safety of targeted therapy Inhibitors for RET-driven Solid Cancer, excluding case reports/series, review papers, meta-analyses, organizational guidelines, editorial letters, expert opinions, and conference abstracts. 15 randomized, locally advanced or metastatic RET-driven solid cancer assays (n=1835) were included. Previously untreated with RET-Specific Tyrosine Kinase Inhibitors(TKI) group showed the highest objective remission rate(ORR) (0.75,95%CI=0.68-0.82) or disease control rate(DCR) (0.96,95%CI=0.92-0.99), and lower dose reduction(34.8%) or discontinuation(3.4%), but the performance of general adverse reactions (Grade1-5 96.8%, Grade3-5 69.2%) were not as good as Multi-Target Tyrosine Kinase Inhibitors (MKI) group, followed by previously treated/untreated with MKI/TKI group (MIX group). Targeted therapy inhibitors have significant efficacy in RET-driven solid cancer therapy. The ORR, DCR parameters and adverse reaction of TKI are better than those of MKI. It was also related to the patient’s previous treatment status. The ORR/DCR of the patients who received no targeted therapy was superior to those who received Vandetanib or Cabozantinib as first-line therapy.