This paper aims to propose a fourth-order matrix spectral problem involving four potentials and generate an associated Liouville integrable hierarchy via the zero curvature formulation. A bi-Hamiltonian formulation is furnished by applying the trace identity and a recursion operator is explicitly worked out, which exhibits the Liouville integrability of each model in the resulting hierarchy. Two specific examples, consisting of novel generalized combined nonlinear Schrödinger equations and modified Korteweg–de Vries equations, are given.