The design and analysis of a paper-based microfluidic analytical device (μPAD) are presented in this paper for the detection of fentanyl and related synthetic opioids. Fentanyl, a synthetic opioid, is an extremely fast-acting synthetic narcotic analgesic having a high potency of approximately 100 to 200 times that of morphine. Detection of fentanyl can be done by colorimetric assays, i.e., spot tests with paper strips and μPADs which offer speed, simplicity of operation, portability, and affordability. The microfluidic behavior of liquid specimen and paper in the μPADs and test strips play a significant role in drug detection methods. Therefore, the study contains the fabrication of the test device using 3D printing and analysis of microfluidic behavior of the paper-based fentanyl test device. A multiphase computational fluid dynamics (CFD) model of a 3D microchannel is developed to evaluate the microfluidic properties. The CFD model incorporates the properties of cellulose and fentanyl solution to determine the flow parameters using the volume of fluid method. Wicking in the cellulose paper is studied analytically considering the Lucas-Washburn equation and Darcy’s law. Experiments with the fabricated μPAD and commercial test-kit samples are also conducted to compare the experimental results with the results for the flow parameters found from the numerical simulation.