<p>In this paper, we focus on the Cauchy problem for the two-dimensional (2D) non-isentropic compressible Navier-Stokes equations with zero thermal conductivity. For the temperature-dependent viscosity coefficients, we establish the local existence and uniqueness of regular solutions with arbitrarily large initial data and far-field vacuum in certain inhomogeneous Sobolev spaces. Several challenges are encountered in this study, including the fact that the appearance of vacuum causes degeneracies in both the time evolution and the spatial dissipation operators, the absence of thermal conduction effects leads to a loss of the smoothing effect, and the critical Sobolev embedding fails. To prove the existence, we first develop an intrinsic singular structure of the nonlinear system by introducing some new variables. Then, based on careful analysis of its intrinsic structure and the characteristics of the special Sobolev embedding in ℝ², we successfully derive some new singular weighted energy estimates, which play an important role in deriving the uniform <i>a priori</i> estimates of the regular solutions. Finally, the well-posedness is established via the standard iterative scheme.</p>