This study addressed five key applications of paper spray mass spectrometry (PS-MS): (i) comparative analysis of the microporous substrate with the cellulose-based substrate in drug detection; (ii) detection of more than 190 fentanyl analogs with their fragmentation pattern can be implemented in the future reference for quicker, accurate and sensitive determination; (iii) exploring sweat in a fingerprint to be considered an alternate method to recognize non-invasive markers of metabolites, lipids, narcotics, and explosive residues that can be used in forensic testing applications; (iv) extending and improving better, cost-effective and quick real-time monitoring of the diseased stage using biofluid samples to obtain vastly different lipid information in viral infection such as COVID-19; and (v) mass spectral detection in chemical warfare agent (CWA) stimulant gas exposure with microporous structure absorbency capabilities in air quality monitoring. This novel synthetic material is known as Teslin® (PPG Industries), consisting of a microporous polyolefin single-layered silica matrix, can be used for precise, sensitive, selective, and rapid sample analysis with PS-MS. The Teslin® substrate provided longer activation time for samples and an active signal with a higher concentration of ion formation and mobility compared to cellulose-based papers. Direct analysis of multiple samples showed that, besides being more sensitive to the study and highly efficient with less sample size and spray solvent needed, Teslin® had less interaction with paper source molecules. For less than 60 seconds of processing time, PS-MS can be used as a rapid detection tool, with limited sample preparation requiring less than one microgram of the sample. Overall, the data in this analysis indicate the capacity of the PS-MS as an alternative approach for direct chemical analysis in many applications. Specifically, the waterproof and microporosity characteristics of Teslin® have proven its usefulness in detecting a variety of chemical components in liquid, solid, and gaseous phases without requiring any chemical treatment or substrate alteration.