The assault was claimed by ethnic Baloch separatists who have hit a string of high-profile targets across the country in recent years, including in the southern port city.
Karachi police chief Ghulam Nabi Memon said the attackers pulled up in a car outside the trading floor and hurled a grenade at the building before opening fire.
Four security guards, a police officer and a bystander were killed in the melee, while local police chief Ghulam Nabi Memon confirmed that all four attackers were also dead.
The Balochistan Liberation Army (BLA) later claimed responsibility in a message sent to AFP, saying an elite unit of fighters had carried out the assault.
The BLA is one of several insurgent groups fighting primarily in Pakistan's southwestern Balochistan province, which has been rocked by separatist and sectarian violence for years.
The group has targeted infrastructure projects along with Chinese workers in Pakistan multiple times in recent years, including during a brazen daylight attack on the Chinese consulate in Karachi which killed four people in 2018.
In May last year, the BLA attacked a luxury hotel near the Afghan border at Gwadar, where a port development is the flagship project of a multi-billion dollar national infrastructure project funded by China.
- Violent history -
Karachi was once a hotspot for crime and violence, with heavily armed groups tied to politicians frequently gunning down opponents and launching attacks on residential areas.
But the situation has largely stabilized in recent years following operations by security agencies against armed political outfits and extremist militants.
The operations were coupled with a series of large-scale military offensives targeting homegrown insurgents as well as Taliban and Al-Qaeda-linked militants -- often based near the lawless border with Afghanistan.
Militant groups still retain the ability to launch periodic attacks in many rural areas of the country.
Monday's attack comes a week after a grenade was thrown at a line of people waiting outside a government welfare office in the city, killing one and injuring eight others, according to a statement from municipal authorities.