Current status and challenges of key physics related to high-confinement operational scenarios and energetic particle confinement are briefly reviewed from the perspective of design and operation of tokamak-based fusion reactors. In the past few decades, significant progress has been made in the research on high-confinement mode physics, i.e. the main stability and confinement constraints on operational window of a fusion reactor have been identified, and some control methods for adjusting plasma kinetic profiles to optimize performance have been developed. Several operational scenarios, including inductive, hybrid and steady-state etc, which are potentially applicable for future reactors, have been developed. In the conditions that fusion alpha particle self-heating is predominant and shear Alfvén wave (SAW) instabilities potentially dominate fusion alpha particle transport, the SAW linear stability properties and excitation mechanisms are understood in depth, and the SAW instabilities nonlinear saturation, alpha particle confinement, and the influence of the heating deposition and the micro-turbulence regulation on fusion profile are under extensive investigation. The magnetically confined fusion research has entered a new stage of ignition and burning plasma physics, and new challenges that are faced are addressed, including whether efficient self-heating of plasmas by fusion alpha particles can be achieved, how the plasma stability and high-confinement can be maintained through the active control of key plasma profiles under the condition of dominant alpha particle heating, and whether it is possible to establish accurate models to predict long time scale complex dynamical evolution of fusion plasmas etc. Solving these key problems will lay a solid scientific foundation for designing and operating future fusion reactors as well as promote the development of plasma science.