This paper presents a novel solution approach for addressing large-scale single-floor process plant layout problems. Based on the mixed-integer linear programming (MILP) representation proposed by Papageorgiou and Rotstein in 1998, the optimal layout (i.e., coordinates and dimensions) is determined through construction-based schemes using mixed-integer optimization. The applicability of the proposed approach is finally demonstrated through four illustrative examples by investigating flowsheets with up to 36 equipment items.