Both work and kinetic energy depend on the reference frame. A ball at rest in one frame has KE = 0; in a moving frame, it has non-zero KE. Work done by a force also differs between frames (displacement differs).

However, the Work-Energy Theorem ($W_{net}$ = $delta_{KE}$) holds in every inertial frame. The relationship is frame-invariant even though individual values are not.

Conservation of energy also holds in any inertial frame, though the numerical value of total energy differs.

For collision problems: work in the center-of-mass frame is simplest. In this frame, total momentum = 0, and the physics is symmetric.