New technologies enable the creation of digital twin systems (DTS) combining continuous data collection from children’s home and artificial intelligence (AI)-based recommendations to adapt their care in real time. The objective was to assess whether children and adolescents with asthma would be ready to use such DTS. A mixed-method study was conducted with 104 asthma patients aged 8 to 17 years. The potential advantages and disadvantages associated with AI and the use of DTS were collected in semi-structured interviews. Children were then asked whether they would agree to use a DTS for the daily management of their asthma. The strength of their decision was assessed as well as the factors determining their choice. The main advantages of DTS identified by children were the possibility to be (i) supported in managing their asthma (ii) from home and (iii) in real time. Technical issues and the risk of loss of humanity were the main drawbacks reported. Half of the children (56%) were willing to use a DTS for the daily management of their asthma if it was as effective as current care, and up to 93% if it was more effective. Those with the best computer skills were more likely to choose the DTS, while those who placed a high value on the physician–patient relationship were less likely to do so. Conclusions: The majority of children were ready to use a DTS for the management of their asthma, particularly if it was more effective than current care. The results of this study support the development of DTS for childhood asthma and the evaluation of their effectiveness in clinical trials.