Current status and challenges of key physics related to high-confinement operational scenarios and energetic particle confinement are briefly overviewed, 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 of high-confinement mode physics, identifying the main stability and confinement constraints on operational window of a fusion reactor, and developing some control methods for tuning plasma kinetic profiles to optimize the performance. Several scenarios, including inductive, hybrid and steady-state scenarios etc, potentially applicable for future reactors, have been developed. In the condition with predominant fusion alpha particle self-heating and shear Alfven wave (SAW) instabilities potentially dominating fusion alpha particle transport, the SAW linear stability properties and excitation mechanisms are well understood, and extensive research has been devoted into the SAW instabilities nonlinear saturation, alpha particle transport, and impact on fusion profile through heating deposition and micro-turbulence regulation. The magnetically confined fusion research has been entering a new stage of ignition and burning plasma physics, and new challenges faced are addressed, including whether efficient self-heating of plasmas by fusion alpha particles can be achieved, how to maintain the plasma stability and high-confinement via 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 issues will lay a solid scientific foundation for designing and operating of future reactors as well as promote the development of plasma science.