Fractional advection-diffusion equation, as a generalization of classical advection-diffusion equation, has been always mentioned to simulate anomalous diffusion in porous media. This work introduces a meshless generalized finite difference method (GFDM) to solve a class of three-dimensional variable-order time fractional advection-diffusion equation (TFADE) in finite domains. Three examples with known analytic solutions in different domains are given to demonstrate that the method is accurate and stable. To reduce computational and storage cost, we discretize the time derivative terms of TFADE by a fast finite difference method (FFDM) based on sum-of-exponentials (SOE) approximation. Meanwhile, discretizing space derivative terms, GFDM generates a linear equation set including function values of neighboring nodes with various weight coefficients. Then the partial derivatives of TFADE are indicated as the linear system above. Also, this paper investigates the irregular mesh in the finite spatial domain, which is more closely meets the description of practice problems. Numerical results indicate that models with irregular mesh can also be simulated by GFDM which maintains high accuracy. Furthermore, the method is stable and accurate in solving three-dimensional irregular domain problems, where the relative errors can be less than 0.01%. This paper shows that FFDM based on SOE approximation can improve computational efficiency, and GFDM can flexibly and efficiently solve three-dimensional variable-order and variable-coefficient TFADE.