The present systematic review and meta-analysis consolidates the available in vitro evidence regarding the impact of selective and combinatorial inhibition of PI3K, AKT, mTOR, as well as dual-targeted molecules, on key functional parameters of RA-FLSs—including proliferation, migration, invasion, cytokine secretion, and the phosphorylation status of pivotal signaling proteins. This evidence concerns the gene PIK3CA and rheumatoid arthritis.