Background: Immunosuppressive therapies are important parts of renal transplantation. Objective: To assess the present literature on the effectiveness of early introduction of mTOR inhibitors with or without calcineurin inhibitors (CNI) in renal transplant recipients in terms of renal functioning and graft survival. Methods: The current literature was reviewed following PROSPERO approval, assessing the role of immunosuppressive agent, mTOR inhibitors as an alternative to CNI within 6 months of renal transplantation by searching PubMed, EMBASE, Cochrane, Crossref, and Scopus. Results: 6 articles of early withdrawal of CNI and introduction of mTOR inhibitors within 6 months of renal transplantation were sought. Glomerular filtration rate (GFR) and serum creatinine were better in mTOR inhibitor group at 12 months. Biopsy-proven acute rejection (BPAR) was significantly higher in mTOR inhibitor group, though survival was comparable. Conclusion: On the basis of present literature, the early introduction of mTOR inhibitors causes substantial CNI minimization. The mTOR inhibitors are more favorable due to their complementary mechanism of action and favorable nephrotoxicity profile, better glomerular filtration, and lower serum creatinine with equivalent survival. However, the higher rejection rate may influence the use of these regimens in patients with moderate to high immunological risk.