Kidney transplantation (KT) is the most effective treatment for end-stage kidney disease. With advancements in modern immunosuppression, graft survival rates for standard-risk recipients have significantly improved, reaching approximately 95% in the first year, 85% at five years, and 65% at ten years. However, long-term outcomes remain challenging due to chronic graft loss and drug-related toxicities. Immunosuppressive drugs, with narrow therapeutic range of safety and efficacy, require drug-monitoring strategies to optimize outcomes. In KT, the standard triple maintenance regimen of tacrolimus, mycophenolate mofetil (MMF), and prednisolone is practiced and MMF is typically administered as a fixed-dose drug. However, evidence suggests that dosage adjustments based on concentration monitoring yield superior clinical outcomes. MMF, an ester prodrug of mycophenolic acid (MPA), necessitates area under the concentration curve (AUC) monitoring due to its complex pharmacokinetics and an exposure level of 30–60 mg/L.h is considered adequate for transplant recipients. However, fixed dosing practices continued, due to controversial evidence and lack of familiarity with AUC and monitoring techniques. AUC monitoring has also been proposed for tacrolimus, a calcineurin inhibitor (CNI), instead of routinely used trough concentration, particularly in "rapid metabolizers" who may experience higher peak concentrations and toxicities. To enhance transplant outcomes, a comprehensive understanding of AUC and relevance to immunosuppressant exposure is critical. This review will primarily focus on MPA AUC exposure in post-kidney transplant patients, explore and explain methods for AUC monitoring, and highlight recent developments in tacrolimus AUC monitoring.