This paper aims to determine the optimum number of RFID readers and their placement for asset tracking. To achieve this goal, an optimization model based on location set covering problem (LSCP) is established. It is implemented in a healthcare facility and the required number of readers for full coverage was determined under certain constraints. This paper is a foremost study which utilizes an enhanced LSCP model for determining the number of RFID readers and their locations. The methodology is original in that it analyzes the tradeoff between cost effectiveness and overall RFID system performance, and provides possible decision guidance to optimize the RFID system. It is vital for healthcare providers to locate crucial assets in the shortest possible time, particularly in emergency situations where human lives are at risk. Hence, increasing the overall RFID system performance will definitely have a valuable effect on real time information sharing, thereby decreasing related search time for crucial assets.