Bui Thi Kieu Loan, 35, Nguyen Hoang Tu, 36, and Pham Dinh Nhan, 43, were carrying two boxes of fruit in Go Vap District on Wednesday morning when caught by local police.
Around 30 kg of meth, 10 kg of ketamine, 4.9 kg of heroin, and 20,000 ecstasy pills were found hidden inside the boxes.
A search of Loan's house revealed more illegal substances.
The investigation is ongoing.
Drug busts and convictions have been frequent in Vietnam despite the country's harsh drug laws.
Those convicted of possessing or smuggling more than 600 grams of heroin or over 2.5 kg of methamphetamine face the death penalty.
The production or sale of 100 grams of heroin or 300 grams of other illegal narcotics is similarly punishable.