Calgary police have laid murder and drug-related charges against four men following a lengthy investigation dubbed Operation Hydra that focused on two unsolved homicides in the city.

Jason Quinn Antonio, 39, died in a northeast Calgary shooting in October, 2014. He had been charged the year before when police seized more than $1 million worth of methamphetamine, cocaine and crack cocaine.

And last May, Taylor John Zanoni, 23, was shot to death in southeast Calgary.

Police have closed off an area around a residence they searched last week in connection with Operation Hydra. (Marc Matulis/CBC)

"Investigators had information that led them to believe both murders were connected to a group of individuals who were heavily involved in drug activity," police said in a release.

Last Friday, Calgary police worked with federal Crown and organized crime prosecutors and the U.S. Drug Enforcement Administration (DEA) in California and Washington to seize 14.2 kilograms of cocaine and 3.2 kilograms of methamphetamine that investigators believe were to be smuggled into Canada.

Insp. Don Coleman said it was a significant quantity of drugs. "Inevitably somebody is going to step up and try to fill the gap," he said.

Subsequent searches carried out in Calgary at four residences and a business resulted in the arrest of four men on Monday, police say.

Gursharanjit Parmar, 32, and Joshua Lloyd Okabe, 30, each face first-degree murder charges in connection with the deaths of Zanoni and Antonio.

Ricco King, 44, and his father William King, 71, were charged with conspiracy to import cocaine.

All four will appear in court in Calgary on July 22.