The continuous change of the drug landscape in the United States demands adaptation and incorporation of emerging analytical methods that preferably allow onsite screening but are also capable of supporting the analysis of seized drugs received at forensic laboratories across the country. Current methods employing color testing require the interaction of chemical reagents with powdered and liquid materials and can often yield inconclusive results, especially when the material is impure. Implementation of portable Raman spectroscopy can remove the need for direct interaction with solid and liquid specimens. In this study a portable, 785 nm, Raman spectroscopy system was employed for screening of seized drug samples, including mixtures. First, a panel of analytes comprised of 15 common drugs of abuse, 15 diluents, and 64 different mixtures comprising various ratios of analytes were used to measure bias, precision, and repeatability in accordance with United Nations Office on Drugs and Crime (UNODC) guidelines for handheld Raman field identification devices for seized material. Accuracy and precision through glass packaging was 91% and 90%; and through plastic was 89% and 88%, respectively for the diluents examined. A subset of the pure and mixture samples was then analyzed using direct analysis in real time mass spectrometry (DART-MS). Identification of analytes was performed manually by observing the [M+H]+ protonated molecule and conducting a library search of an in-house database. Using DART-MS, the drug analyte present in the sample was correctly identified 92% of the time using the library search feature. The presence of dimers and –OH losses were also observed for many of the analyte drugs of abuse. The combination of portable Raman spectroscopy and DART-MS data resulted in an overall accuracy of 96% for the detection of both drugs and diluents. The combined accuracy when analyzing authentic case samples was 83%, providing a rapid and accurate method for seized drug screening within drug chemistry laboratories.