Summary: In this paper, we propose and study a unified mixed-integer programming model that simultaneously optimizes fluence weights and multi-leaf collimator (MLC) apertures in the treatment planning optimization of VMAT, Tomotherapy, and CyberKnife. The contribution of our model is threefold: (i) Our model optimizes the fluence and MLC apertures simultaneously for a given set of control points. (ii) Our model can incorporate all volume limits or dose upper bounds for organs at risk (OAR) and dose lower bound limits for planning target volumes (PTV) as hard constraints, but it can also relax either of these constraint sets in a Lagrangian fashion and keep the other set as hard constraints. (iii) For faster solutions, we propose several heuristic methods based on the MIP model, as well as a meta-heuristic approach. The meta-heuristic is very efficient in practice, being able to generate dose- and machinery-feasible solutions for problem instances of clinical scale, e.g., obtaining feasible treatment plans to cases with 180 control points, 6750 sample voxels and 18,000 beamlets in 470seconds, or cases with 72 control points, 8000 sample voxels and 28,800 beamlets in 352seconds. With discretization and down-sampling of voxels, our method is capable of tackling a treatment field of \(8000 - 64, 000 \operatorname{cm}^3\), depending on the ratio of critical structure versus unspecified tissues.