I am familiar with the decline of the city of Rome during the 3rd-century crisis and the late Roman empire in favor of cities like Ravenna and Constantinople, as well as the 410 CE sack of Rome ad the city's constant changing of hands during wars between the Byzantines and Ostrogoths.
However, as far as I am aware, besides it's cultural and religious significance, Rome was one of the smaller and weaker cities on the Italian peninsula, compared those in the north like Florence, Venice, and Milan, throughout the middle ages and early modern era. Correct me if I am wrong but didn't the city only begin to grow to its current size after Italian unification when Rome was made the capital.
If Rome was able to become a relatively large and powerful regional city by the time of the Punic Wars and then one of the biggest in the world by the height of the empire, why did was Rome not able to bounce back substantially during the ~14 centuries between its heavy depopulation and it being made the capital of the kingdom of Italy?
Rome is not very strategically significant, being so far down the peninsula. You mentioned Venice, Milan, and Florence. All are much closer to the sea or the rest of Europe. Rome was also systematically stripped of much of its wealth. Particularly in the Visigoth raid of 455 (which was far worse than 410 raid) and the Vandalic Wars shattered the city's aqueducts. Given where Rome is located, those aqueducts were essential to maintaining a large population. Bringing in water from higher elevations was crucial to reduce the risk of malaria, and they could not do this without aqueducts.
Also, the size and scale of the old Roman Republican/Imperial architecture often worked against the city. When things were damaged in earthquakes, the cost and difficulty to repair them seemed astronomical to a city that no longer received tax revenue from most of the known world, as a result taking the damaged buildings apart for building materials was particularly common in Rome.
Rome also had the unfortunate luck to be far enough from the sea not to be a thriving port city, but close enough to be vulnerable to raids from naval forces. The Arabs did this successfully in the 9th century
Also, Rome began to recover far earlier than the Italian Unification. Rome recovered during the Renaissance to become the main city for artists during the 15th century, and a series of strong popes with deep purses funded building and restorations during this time.