Security, sovereignty, tariffs, trade, drugs and migration — all hot-button issues for the Trump administration and its neighbors in the Western Hemisphere — will top Secretary of State Marco Rubio's agenda this week on his third trip to Latin America since becoming the chief U.S. diplomat.

In talks with leaders in Mexico and Ecuador on Wednesday and Thursday, Rubio will make the case that broader, deeper cooperation with the U.S. on those issues is vitally important to improving health, safety and security in the Americas and the Caribbean.

Yet, Trump has alienated many in the region — far beyond the usual array of U.S. antagonists like Cuba, Nicaragua and Venezuela — with persistent demands, coupled with threats of sweeping tariffs and massive sanctions for not complying with his desires.

Shortly before Rubio left for Mexico on Tuesday, he and Trump announced the U.S. military had carried out a strike in the southern Caribbean against a drug-carrying vessel that departed from Venezuela as part of recent deployments to combat threats from Latin American drug cartels.

Rubio said in a post on X the vessel was being operated by a “designated narco-terrorist organization” and described the operation as a lethal strike.