To faithfully simulate ITER and other modern fusion devices, one must resolve electron and ion fluctuation scales in a five-dimensional phase space and time. Simultaneously, one must account for the interaction of this turbulence with the slow evolution of the large-scale plasma profiles. Because of the enormous range of scales involved and the high dimensionality of the problem, resolved first-principles global simulations are very challenging using conventional (brute force) techniques. In this thesis, the problem of resolving turbulence is addressed by developing velocity space resolution diagnostics and an adaptive collisionality that allow for the confident simulation of velocity space dynamics using the approximate minimal necessary dissipation. With regard to the wide range of scales, a new approach has been developed in which turbulence calculations from multiple gyrokinetic flux tube simulations are coupled together using transport equations to obtain self-consistent, steady-state background profiles and corresponding turbulent fluxes and heating. This approach is embodied in a new code, Trinity, which is capable of evolving equilibrium profiles for multiple species, including electromagnetic effects and realistic magnetic geometry, at a fraction of the cost of conventional global simulations. Furthermore, an advanced model physical collision operator for gyrokinetics has been derived and implemented, allowing for the study of collisional turbulent heating, which has not been extensively studied. To demonstrate the utility of the coupled flux tube approach, preliminary results from Trinity simulations of the core of an ITER plasma are presented.