The royal couple will join children, parents, carers and celebrity supporters a the glittering ceremony at the Royal Lancaster Hotel in London on Tuesday.
Prince Harry has been patron of WellChild - the national charity for seriously ill children and their families - since 2007.
But it will be the first time that his wife Meghan accompanies him to the event.
The duke and duchess will attend a pre-ceremony reception and meet the young winners of each award category and their families, and the nominated healthcare professionals.
Harry will present an award during the ceremony and also deliver a speech.
Winners this year include seven-year-old Matilda Booth, from Sowerby Bridge in West Yorkshire, who has spina bifida, is paralysed from the chest down and has had more more than 40 operations.
She has been praised for her "great zest for life" and her "courage, strength and determination".
Mckenzie Brackley, from Fife, has also been hailed as inspirational.
The four-year-old, who had to learn to speak, swallow, eat and drink and move again due to acute flaccid paralysis, was praised for being there for other children when they are scared or sad.
"Despite his own problems Mckenzie cheers up everyone when they are low, and is guaranteed to put a smile on your face," WellChild said.