The structural responses of in¯lled frames subjected to combined in-plane and out-of-plane loadings are usually analyzed by separately applying in-plane and out-of-plane loads. The interaction e®ect of in-plane and out-of-plane loads on the structural behavior of the frames is ignored; thus errors in predicting the actual force-transfer mechanisms and modes of failure of the structures can be incurred. To solve the problem, this paper presents a discrete¯nite element modeling technique, which employs a damage-based cohesive crack representation of fracture behavior of masonry in¯lls, followed by a study on the force-transfer mechanisms and failure modes of the anchored and unanchored in¯lled reinforced concrete (RC) frames subjected to interactive in-plane and out-of-plane loads. The analysis indicates that under out-ofplane loading the diagonal compressive thrust of masonry-in¯ll walls, which is induced by in-plane lateral loading and acts on the walls, may reduce the in-plane load capacity of the RC frame by up to 50% and cause buckling of in¯ll walls. On the other hand, the anchorage can e®ectively prevent the separation of in¯ll walls from the bounding frame and provide stabilizing forces to the walls against buckling.