I am going to try and define this by a couple of different aspects, physical, pedagogy and motivation.
Physical: Ironically I think in some ways this is the easiest to change, but often creates some of the biggest concerns. The concept of "seat time" would be eliminated and the content would not be limited to a specific space in the building (or even in the building for that fact). The physical space would be determined by the learning project/need rather than "math room" or "lab". I think this is a great example of thinking outside the box in terms of space. http://www.usatoday.com/story/sponsor-story/xq/2017/02/14/high-school-educate-students-most-unlikely-place/97703092/
Pedagogy: This creates a greater challenge. Because subjects are not taught in isolation, but in a interdisciplinary topical approach, it requires greater skill of teachers to be able to recognize the learning connected to standards. As a teacher, not only do I have to have an incredible understanding of my content standards, and learning outcomes for students, but I also have to have some interdisciplinary understanding as well. It would also require more collaboration and co-teaching to provide that.
Motivation: I think this might be the biggest challenge. People need a voice and choice in their learning. I was talking with a high school girl who was in an AP chemistry course. She was taking it because she wanted to be a pharmacist an would look good on a transcript for colleges. She described the class as "same as regular with more homework". It was just the better hoop to jump through. With her interest in pharmaceuticals, think of the potential projects she could have created that could have been just as or even more challenging and so much more meaningful to her.