I do not think that Who's the Boss reboot would work now.

Personally, I think it is very hard to see her as Samantha again. It is like the Whoopi Goldberg effect with the View. When we hear too much of someone in real life , it just breaks the illusion. She became more of a reality/social media personality now. When I see her in films I now thing "Ho here is Alyssa Milano, sorry not sorry gal from the internet that wanted Shannen doherty fired and who sets up a go fund me for her kid although she is rich" . I used to like Samantha Micelli but now that I am so familiar with Alyssa Milano even watching Whos the boss do not feel quite the same.