According to the American Society of Anesthesiologists Closed Claims Database, one of three drug-related errors is the result administrating an incorrect dose. Directly measuring drug concentration removes the uncertainty in the dose-concentration relationship and addresses inter- and intra-subject variabilities that affect the pharmacokinetics of anesthetics. Here we describe a dual-analyte microcatheter-based electrochemical sensor capable of simultaneous real-time continuous monitoring of fentanyl (FTN) and propofol (PPF) drugs simultaneously in the operating rooms. Such a dual PPF/FTN catheter sensor relies on embedding two different modified carbon paste (CP)-packed working electrodes along with Ag/AgCl microwire reference electrodes within a mm-wide Teflon tube, and uses a square wave voltammetric (SWV) technique. The composition of each working electrode was judiciously tailored to cover the concentration range of interest for each analyte. A polyvinyl chloride (PVC) organic polymer coating on the surface of CP electrode enabled selective and sensitive PPF measurements in μM range. The detection of nM FTN levels was achieved through a multilayered nanostructure-based surface modification protocol, including a CNT-incorporated CP transducer modified by a hybrid of electrodeposited Au nanoparticles and electrochemically reduced graphene oxide (erGO) and a PVC outer membrane. The long-term monitoring capability of the dual sensor was demonstrated in a protein-rich artificial plasma medium. The promising antibiofouling behavior of the catheter-based multiplexed sensor was also illustrated in whole blood samples. The new integrated dual-sensor microcatheter platform holds considerable promise towards real-time, in-vivo detection of the anesthetic drugs, propofol and fentanyl, during surgical procedures towards significantly improved safe delivery of anesthetic drugs. © 2020 Elsevier B.V.