'In the South of' is like a prepositional case usage where the place is located in the south of that particular country/location. Odesa is located in the south of Ukraine.
'To the south of' is in reference to another location. Bulgaria is located to the south of the Ukraine. Bulgaria is not in the south of Ukraine.
Out of curiosity, from DeepL translator, it looks like both of these types of descriptions in Ukrainian use prepositional case (or at least, I think so, maybe 'на південь від України' here has a directional aspect?):
Одеса розташована в південній частині України. Болгарія розташована на південь від України.
In Russian, the distinction between the two is more analogous to English: 'located to the south of' takes the dative and then the genitive 'к югу от' and 'located in the south of' takes the prepositional case 'в.'
Одеса находится в Южной Украинe. Болгария находится к югу от Украины