The four young men were driving through Colonia Paseo Residencial, a neighborhood in the southern section of Monterrey, when the gunmen opened fire on them from another vehicle.
Misael Vazquez Salazar and Cristian Ubaldo Cantu Martinez, both 17, died in the attack, relatives said.
A 20-year-old man and a 16-year-old boy wounded in the attack were transported to a hospital for treatment.
The motive for the attack is not known, officials said.
Monterrey, Mexico's most important industrial city, and its suburbs have been battered by a wave of drug-related violence since March 2010, when three rival cartels reportedly went to war with Los Zetas, considered the country's most violent criminal organization.
Los Zetas has been battling an alliance of the Gulf, Sinaloa and La Familia drug cartels, known as the Nueva Federacion, for control of the Monterrey metropolitan area and smuggling routes into the United States.
Heriberto Lazcano Lazcano, known as "El Lazca," deserted from the Mexican army in 1999 and formed Los Zetas with three other soldiers, all members of an elite special operations unit, becoming the armed wing of the Gulf drug cartel.
After several years on the payroll of the Gulf cartel, Los Zetas, considered Mexico's most violent criminal organization, went into the drug business on their own account and now control several lucrative territories.
A total of 267 murders were registered in the industrial city in 2009, with the figure rising to 828 in 2010 and more than 1,100 so far this year, according to official figures.