"We have taken a new approach, which is creating not only specialized units that focus on particular products or markets or transactions but we've hired private sector consultants … to bring their expertise to bear," Khuzami told CNBC in an interview on Wednesday.
"There's always unfinished business, but the SEC and division of enforcement is poised perhaps as never before to take on the challenges of the future and whatever products or markets or transactions develop going forward," he said.
Khuzami is the latest in a series of high-profile officials to step down from the SEC since President Barack Obama won re-election in November, including SEC Chairman Mary Schapiro and the two directors of other divisions that oversee markets and public company disclosures.
The SEC did not name a replacement for Khuzami, and it did not say what he plans to do after his departure, expected at the end of the month.
Agency insiders say possible candidates to replace Khuzami could include the SEC's deputy enforcement director, George Canellos, and the regional director of the SEC's Boston office, David Bergers.
Khuzami, a former federal prosecutor in the U.S. attorney's office for the Southern District of New York, was tapped by Schapiro in early 2009 as the SEC was still reeling from the fall-out of missing Bernard Madoff's massive $65 billion Ponzi scheme.
The scheme went undetected by the SEC despite numerous red flags going back to the early 1990s. The Madoff miss, along with problems in the SEC's oversight leading up to the 2007-2009 financial crisis, raised questions about the agency's credibility and willingness to crack down on wrongdoers.
Khuzami was hired in large part due to his experience with prosecuting high-profile cases, from the conviction of "Blind Sheik" Omar Abdel Rahman to trying 11 defendants in U.S. v. Bennett — a $1 billion Ponzi scheme case.
"I have spent half my career in public service, and nowhere is there the level of professionalism, skill, and talent on such a large and coordinated scale as there is in the SEC's Division of Enforcement," Khuzami said in a statement. "They have inspired me, educated me, and motivated me to do my very best."