The second-order serendipity virtual element method is studied for the semilinear pseudo-parabolic equations on curved domains in this paper. Nonhomogeneous Dirichlet boundary conditions are taken into account, the existence and uniqueness are investigated for the weak solution of the nonhomogeneous initial-boundary value problem. The Nitsche-based projection method is adopted to impose the boundary conditions in a weak way. The interpolation operator is used to deal with the nonlinear term. The Crank-Nicolson scheme is employed to discretize the temporal variable. There are two main features of the proposed scheme: (i) the internal degrees of freedom are avoided no matter what type of mesh is utilized, and (ii) the Jacobian is simple to calculate when Newton’s iteration method is applied to solve the fully discrete scheme. The error estimates are established for the discrete schemes and the theoretical results are illustrated through some numerical examples.