Service with France
For the rest of 1642 and part of the 1643 campaigns, Thomas commanded Piedmontese forces fighting alongside the French under Henri d'Orléans, Duke of Longueville against the Spanish, generally along the Piedmont/Milan border; when Longueville was recalled home, Thomas succeeded him as allied commander-in-chief, with Turenne as his second-in-command. (Thomas was given the supreme command only because of his birth; another French general, Du Plessis Praslin, noted a few years later that French marshals would only serve under someone who was superior to them in social rank, and Thomas, with his blood relationship to the French and Spanish royal families, was the only candidate.) By late summer, both Thomas and Turenne were seriously ill and Du Plessis Praslin was in temporary command. Thomas led the joint armies again in 1644, taking Santya and Asti; he also tried to take Finale Ligure, but gave up the attempt, apparently because he feared this valuable port would end up in French control rather than Piedmontese. In 1645, now commanding with Du Plessis Praslin, he took Vigevano, but was defeated at the River Mora. In 1646, Thomas was put in command of the French expedition sent south to take the Tuscan forts, after which he was to advance further south to Naples, drive out the Spanish and put himself on the throne of the kingdom; but the expedition set off late, and when he besieged Orbetello, the supporting French fleet was defeated by the Spanish and he was forced to raise the siege and conduct a difficult retreat, which he performed so poorly that Cardinal Mazarin subsequently despised his command ability, viewed him as incompetent, and declined to appoint him to the expedition that France sent to support the Naples revolt late in 1647 (this did not stop Mazarin from considering him as a potential candidate for a French-backed King of Naples, though Paris was so slow to move on this that Henry II, Duke of Guise was adopted by the Neapolitans instead). In the 1647 campaign, Thomas is mentioned as commanding alongside the French general in the forces sent across north Italy to work with the Duke of Modena Francesco I d'Este who had just allied with France and opened up a 'second front' against the Spaniards in Milan, though Mazarin confessed that he had appointed Thomas only because he feared that, if left behind in Piedmont, the Prince's restless spirit would make more trouble. By spring of 1648 however he was back in Piedmont, fighting on the Piedmont-Milan border to distract the Spanish from their pressure on Modena; in the summer, he was put in charge of an army sent on a fleet to Naples - the Naples revolt had already collapsed by then, so the expedition found no support when it landed and after some pointless actions it re-embarked, a complete failure (some details in Naples revolt). On his return with the French fleet, Thomas was delayed in Provence and unable to join the great siege of Cremona where he was expected.
During his absence, Regent Christine had gained control of the fortresses granted to Thomas as part of the settlement of the Piedmontese Civil War (legally, these reverted to ducal control when the Duke came of age), which under Piedmontese law Charles Emmanuel did in 1648, though his mother remained in control of the government; Christine, accompanied by her son and part of the ducal army, entered Ivrea and dismissed Thomas' personal garrison; she appointed Thomas instead as governor or Asti and Alba, positions which sweetened the blow but were entirely under ducal control, not guaranteed by treaty. When he returned to Piedmont, Thomas had no choice but to accept the fait accompli, and soon after this he went to live in Paris.
During the Fronde, Thomas linked himself closely with Cardinal Mazarin, who, although effectively prime minister of France, was like him an Italian outsider at the French court. In the early 1650s, Thomas was seen as an important member of Mazarin's party, closely linked to the Cardinal, regularly seen in conference with him, and active in his support. In 1651 when Mazarin had been forced into exile, the Prince was for a time brought onto the conseil du roi, and an (admittedly very hostile) contemporary the duchesse de Nemours described him as a 'prime minister without being aware of it'; there were suggestions that Mazarin's opponents within the court had raised him up as a rival to the cardinal with the Queen, but this is unlikely, especially since Mazarin himself urged the Queen to follow Thomas' advice, and it is more probable that Mazarin backed the Prince as someone who would keep other rivals from gaining control in his absence but who would never have the status within France to set himself up as a permanent replacement for the Cardinal. By the time Mazarin returned from his second and last exile in February 1653, Thomas, who accompanied the court to St Denis to welcome the Cardinal home, was insignificant again - an analysis of Mazarin's close colleagues at this time by the later historian Chéruel made no mention of him. In January 1654, when the last of the ceremonial offices formerly belonging to the rebel leader Louis II de Bourbon, Prince de Condé were disposed of, Prince Thomas was made Grand Maitre.
The Franco-Spanish war had been continuing in north Italy, and late in 1654, increasing Piedmontese hostility to the current French commander Grancey led to a search for a new allied commander-in-chief; the French would have preferred to send the Duke of York (later King James II), but he too was unacceptable to Turin, so Thomas was appointed as joint commander - though his wife was held in France almost as a hostage for his good behaviour. On 16 December 1654 he arrived in Turin, to a ceremonial welcome by the French troops and an unexpectedly friendly reception by Charles Emmanuel. On 4 April 1655 Thomas Francis commanded the Waldensians to attend Mass or remove to the upper valleys, giving them twenty days in which to sell their lands. The Duke of Savoy sent an army, and on 24 April, at 4 a.m., the signal was given for a general massacre so brutal that it aroused indignation throughout Europe. Oliver Cromwell began petitioning on behalf of the Vaudois, and John Milton wrote his famous poem about this, "On the Late Massacre in Piedmont." In the 1655 campaign, he led an invasion of the Duchy of Milan, though already ill with malaria, and besieged Pavia, where the attack went so badly that he was forced to leave his sick-bed to take direct control of the siege, and even then it had to be raised after nearly two months of fruitless effort.