Maria Theresa, Charles VI's heiress, was at the center of his plans of what might happen following his eventual demise.
While there were plans dating back to 1703 that discussed contingency plans if the male Habsburg line was to die out: mainly granting succession rights to Joseph I's daughters as well as any future female issue that Charles VI might have, with Joseph's daughters taking precedence. When Charles VI succeeded his brother, he wanted to amend these plans to give his own daughters preference. This was done secretly and led to what became known as the Pragmatic Sanction. For over a decade, Charles VI labored to secure diplomatic recognition for the Pragmatic Sanction among the Courts of Europe, and also worked towards securing a marriage for his heiress, Maria Theresa. His initial plans always centered upon the House of Lorraine: Maria Theresa's first potential suitor was to Léopold Clément, heir to the Duchy of Lorraine. He was supposed to be sent to Vienna in 1723 to finish his education, but he died. Léopold was eventually exchanged for his younger brother, François Étienne / Francis Stephen—who eventually married Maria Theresa in 1736 and would become Holy Roman Emperor in 1745.
Though Lorraine was the most popular idea, Charles VI considered other possibilities. One idea that has been popularly explored in Alternate History was the possibility of a match between Frederick the Great and Maria Theresa—Frederick himself apparently proposed himself as a possible candidate in exchange for giving up his succession rights. Religious differences also plagued the possibility of such a match. Aside from that, Elisabeth Farnese expressed interest in a rapprochement with Austria and proposed that the Infante Carlos (OTL Charles III of Spain) should marry Maria Theresa while the Infante Felipe (OTL Philip of Parma) should marry Maria Anna. Charles and Maria Theresa was allegedly betrothed in 1725, but it was eventually broken off—probably sometime in 1729.
Now, what if the betrothal held? Let's just say for whatever reason that Charles VI is adamant that this is the best way forward—maybe he's just not that impressed with François Étienne, or for whatever other reason you choose. In 1725 Carlos was behind his brother Fernando in the Spanish Succession, and his mother Elisabeth Farnese had managed to secure the right for Carlos to succeed to Parma following the death of Francesco and Antonio Farnese. You would likely need something to bump Carlos further down within the Spanish Succession, as I'm sure none of the European Powers would accept the idea of Carlos being wed to the Austrian heiress when he's literally a heartbeat away from the Spanish throne. Ideally that would be Barbara of Portugal having children with Fernando VI: such as Barbara's pregnancy in 1733 being successful (IOTL, she had a stillborn son). If they can have a few more children, even better.
What sort of effects might this have going forward? Italy seems to be the place that have the most immediate effects: how do things play out if Carlos is still engaged to Maria Theresa and in effect being groomed to become the next Holy Roman Emperor? Carlos was accepted as heir of Tuscany in 1718, but he didn't enjoy universal recognition. I imagine Charles VI's tune might change if Maria Theresa remains engaged to him, but I imagine other European powers might object instead, as Tuscany + Parma eventually passing into Austrian hands means that almost the whole of Italy would be under Austrian influence. I suppose the most likely plan is that Carlos might be swapped out as heir for Tuscany for his younger brother, Felipe. The only other idea was unpopular and enjoyed almost no support: that Gian Gastone would be succeeded by his sister, Anna Maria Luisa—who in 1729 is a 62 year old woman, a widow with no children, meaning that the problem is only being kicked down the hallway for someone else to deal with when she eventually dies.
Aside from that, there would certainly be huge effects in Spain aligning themselves with the Austrians—especially where it concerns conflicts in the 1730s and 1740s and diplomatic relations. An Austro-Spanish alliance that holds might preclude reconciliation between the French and Spanish branches of the Bourbons, and will likely have other diplomatic knock-off effects among the stately quadrille: no Anglo-Austrian alliance, and perhaps even causing the Anglo-French alliance to endure beyond 1731: especially if French politicians see the possible union of Carlos + Maria Theresa as a revival of the Habsburg encirclement of the 16th + 17th centuries, they might see more interest in maintaining good relations with Britain, and the British may as well: there were certainly some within British political circles who espoused Francophile views and saw French military / cultural domination in Europe as inevitable. If French and Britain do not remain formally allied, they may have better relations, though of course their issues in the wider world might preclude that. Conflicts such as the War of the Polish Succession and eventual War of the Austrian Succession would likely have much different alliance lineups and play out quite differently, too.
While there were plans dating back to 1703 that discussed contingency plans if the male Habsburg line was to die out: mainly granting succession rights to Joseph I's daughters as well as any future female issue that Charles VI might have, with Joseph's daughters taking precedence. When Charles VI succeeded his brother, he wanted to amend these plans to give his own daughters preference. This was done secretly and led to what became known as the Pragmatic Sanction. For over a decade, Charles VI labored to secure diplomatic recognition for the Pragmatic Sanction among the Courts of Europe, and also worked towards securing a marriage for his heiress, Maria Theresa. His initial plans always centered upon the House of Lorraine: Maria Theresa's first potential suitor was to Léopold Clément, heir to the Duchy of Lorraine. He was supposed to be sent to Vienna in 1723 to finish his education, but he died. Léopold was eventually exchanged for his younger brother, François Étienne / Francis Stephen—who eventually married Maria Theresa in 1736 and would become Holy Roman Emperor in 1745.
Though Lorraine was the most popular idea, Charles VI considered other possibilities. One idea that has been popularly explored in Alternate History was the possibility of a match between Frederick the Great and Maria Theresa—Frederick himself apparently proposed himself as a possible candidate in exchange for giving up his succession rights. Religious differences also plagued the possibility of such a match. Aside from that, Elisabeth Farnese expressed interest in a rapprochement with Austria and proposed that the Infante Carlos (OTL Charles III of Spain) should marry Maria Theresa while the Infante Felipe (OTL Philip of Parma) should marry Maria Anna. Charles and Maria Theresa was allegedly betrothed in 1725, but it was eventually broken off—probably sometime in 1729.
Now, what if the betrothal held? Let's just say for whatever reason that Charles VI is adamant that this is the best way forward—maybe he's just not that impressed with François Étienne, or for whatever other reason you choose. In 1725 Carlos was behind his brother Fernando in the Spanish Succession, and his mother Elisabeth Farnese had managed to secure the right for Carlos to succeed to Parma following the death of Francesco and Antonio Farnese. You would likely need something to bump Carlos further down within the Spanish Succession, as I'm sure none of the European Powers would accept the idea of Carlos being wed to the Austrian heiress when he's literally a heartbeat away from the Spanish throne. Ideally that would be Barbara of Portugal having children with Fernando VI: such as Barbara's pregnancy in 1733 being successful (IOTL, she had a stillborn son). If they can have a few more children, even better.
What sort of effects might this have going forward? Italy seems to be the place that have the most immediate effects: how do things play out if Carlos is still engaged to Maria Theresa and in effect being groomed to become the next Holy Roman Emperor? Carlos was accepted as heir of Tuscany in 1718, but he didn't enjoy universal recognition. I imagine Charles VI's tune might change if Maria Theresa remains engaged to him, but I imagine other European powers might object instead, as Tuscany + Parma eventually passing into Austrian hands means that almost the whole of Italy would be under Austrian influence. I suppose the most likely plan is that Carlos might be swapped out as heir for Tuscany for his younger brother, Felipe. The only other idea was unpopular and enjoyed almost no support: that Gian Gastone would be succeeded by his sister, Anna Maria Luisa—who in 1729 is a 62 year old woman, a widow with no children, meaning that the problem is only being kicked down the hallway for someone else to deal with when she eventually dies.
Aside from that, there would certainly be huge effects in Spain aligning themselves with the Austrians—especially where it concerns conflicts in the 1730s and 1740s and diplomatic relations. An Austro-Spanish alliance that holds might preclude reconciliation between the French and Spanish branches of the Bourbons, and will likely have other diplomatic knock-off effects among the stately quadrille: no Anglo-Austrian alliance, and perhaps even causing the Anglo-French alliance to endure beyond 1731: especially if French politicians see the possible union of Carlos + Maria Theresa as a revival of the Habsburg encirclement of the 16th + 17th centuries, they might see more interest in maintaining good relations with Britain, and the British may as well: there were certainly some within British political circles who espoused Francophile views and saw French military / cultural domination in Europe as inevitable. If French and Britain do not remain formally allied, they may have better relations, though of course their issues in the wider world might preclude that. Conflicts such as the War of the Polish Succession and eventual War of the Austrian Succession would likely have much different alliance lineups and play out quite differently, too.