On 7 December 2004, Toledo returned to Groton, Connecticut, after a six-month deployment in the Persian Gulf with the John F. Kennedy Carrier Strike Group that included port calls in Crete, Dubai, and Bahrain.

Once back in the North Atlantic, she was diverted for a classified drug interdiction mission with the Joint Interagency Task Force–South in the Caribbean Sea.

Ports of call included Augusta Bay, Sicily, Dubai, the British Indian Ocean Territory of Diego Garcia, and La Maddalena.

On 20 January 2011, Toledo returned to Groton, Connecticut, after a six-month deployment that included port calls in Cyprus, Bahrain, and Haifa.

On 12 September 2019, Toledo completed an eight-month EUCOM deployment that included port calls in Faslane, Scotland and Haakonsvern, Norway.

In early 2020, YouTuber and science communicator Destin Sandlin travelled aboard Toledo for 24 hours as part of a video series profiling different features and functions of the submarine.