Stolfo is regarded as creating the area of machine learning applied to intrusion detection and has created several anomaly-detection algorithms and systems addressing some of the hardest problems in securing computer systems. Of particular note is his interest in detecting zero-day attacks and credential theft. Stolfo is also co-inventor of a novel technology that automatically injects intrusion detection functionality into arbitrary special-purpose embedded devices. Stolfo has been granted over 60 patents.

Stolfo received a BS in Computational Information Sciences from Brooklyn College, CUNY, in 1975 and a PhD in Computer Science from Courant Institute, New York University, in 1979.