With Afghanistan off-limits, a paranoid Turkmenistan and only 1 open border crossing into Tajikistan, the southern regions of Qashqadaryo and Surxondaryo are a cul-de-sac. Not on the way to anywhere else, the people who make it this far are the dedicated travelers.
Visiting Qashqadaryo and Surxondaryo (these are the new Uzbek spellings) is still difficult. Special permits are sometimes needed for the Buddhist monasteries near the Afghan border, and the Gissar mountains straddling the border with Tajikistan are patrolled and possibly still booby-trapped from the civil war in the 90’s.
So this is real, old-school Central Asia travel. Locals are surprised at seeing a foreigner, and small-town police assumes you are a spy.
With actually interesting museums, archaeological sites of Buddhist ancestry and relics from Soviet and medieval times (like the Jarkurgan minaret), Termez should be the main tourist attraction of the region. Its out-of-the-way location means Shahrisabz gets way more tourists.
The seat of power of Tamerlane, Shahrisabz got bulldozed in 2015 and is still in a state of reconstruction. You can however, visit the main monuments and get some really good deals on embroidered textiles, for which the town is famous.
Urgut is a quiet village near the mountains where the weekly market is of interest. The vast majority is of course nothing but Chinese goods and carrot and potato, but a section of suzani sellers has real treasures on offer. It is a good reason to get out of Samarkand without having to visit more ancient buildings.
The main attraction of little-visited Qashqadarya and Surxondarya is exploration. Go beyond the guidebook, and dig into the local culture of this Tajik-dominated area. For instance, unable to pick out 1 single thing, UNESCO put the whole cultural space of Boysun district on their Intangible Heritage List.
Little villages like Katta Langar, for instance: there are hundreds. Perhaps trek into the Langar valley to the observatory and ask for a place to stay from the astronomers?
There is still so much beauty in the south, unknown to any guidebook. Did you know about the Dark Star, perhaps the world’s deepest cave? I didn’t.
Sangardak (named after the 150m-high Sangardak waterfall) is a group of young people trying to promote ecotourism in the region.
You might be headed to Denau, where you can cross the border into Tajikistan. From the border, it isn’t far to Dushanbe, in the heart of the Karotegin region. If not, return to the rest of Uzbekistan or continue to Mazar-i-Sharif in Afghanistan.