The chronic, relapsing nature of tobacco use represents a major challenge in smoking cessation treatment. Recently, novel intervention paradigms have emerged that seek to adjust treatments over time in order to meet a patient's changing needs. This article demonstrates that Hybrid Model Predictive Control (HMPC) offers an appealing framework for designing these optimized, time-varying smoking cessation interventions. HMPC is a particularly appropriate approach as it recognizes that intervention doses must be assigned in predetermined, discrete units while retaining receding-horizon, constraint-handling, and combined feedback and feedforward capabilities. Specifically, an intervention algorithm is developed here in which counseling and two pharmacotherapies are manipulated to reduce daily smoking and craving levels. The potential usefulness of such an intervention is illustrated through simulated treatment of a quit attempt in a hypothetical patient, which highlights that prioritizing reduction in craving over total daily smoking levels significantly reduces craving levels, suppresses relapse, and successfully rejects time-varying disturbances such as stress, all while adhering to several practical operational constraints and resource use considerations.