The Turtles have fallen on hard times since their last adventure in 1990. They've all fallen victim to substance abuse problems as well as drugs and homelessness. But when Splinter dies (a death in the family) Donatello (now an entrepreneur and writer) brings his brothers back together to help them get back on their feet
This is sort of a joke but I'd actually love to see a Logan-style sequel to the original movie. Showing the aged Turtles at their lowest points, coming back together to mourn Splinter as a the Foot (led by Karai) take over NYC once again. They could adapt City At War