Thomas Jefferson certainly faced many obstacles, which should not be surprising for a leader of a revolution and founder of a nation. The other educator mentions some great examples. I will mention a couple more you might consider that occurred during his presidency.
When he was president, Jefferson really wanted to expand the country's role in international commerce. Unfortunately, the Barbary pirates of North Africa were seizing American ships and demanding huge tributes. In fact, in 1800, twenty percent of the federal budget went to paying pirates. The next year the United States fought its first foreign war against the Barbary pirates in order to end this tribute system. This meant building and outfitting a sufficient navy for the young country.
Back at home, Jefferson faced the embarrassing trial of Aaron Burr, his former vice president. It had come to light that Burr was conspiring to seize land in the southwest of the country and part of Mexico and might be establishing an independent nation. Jefferson was compelled to issue a warrant for Burr's arrest and charge him with treason. Ultimately, Burr was left uncharged, as there was not enough evidence to convict him. This was a political embarrassment for the Jefferson administration but it did negate any future political aspirations of Burr.