Purpose of Review <p>This narrative review examines lifestyle considerations before, during, and after second-generation obesity management medication (OMM) treatment.</p> Recent Findings <p>Second-generation OMMs, including semaglutide and tirzepatide, have demonstrated unprecedented weight losses of around 15–20% in recent trials, leading to their swift uptake in clinical care. With increased pharmacotherapy effectiveness, attention has shifted to the accompanying role of lifestyle interventions in optimizing health and wellbeing. Emerging literature raises concerns regarding treatment sustainability, lean mass loss, nutritional risks, and weight regain following pharmacotherapy discontinuation, highlighting persistent gaps in the role of lifestyle strategies during OMM treatment.</p> Summary <p>Lifestyle modification remains the cornerstone of obesity treatment, yet barriers to implementation and long-term success underscore the need for more sustainable strategies. As novel OMMs redefine obesity care, lifestyle programs may be able to shift focus from weight reduction to overall health promotion. However, the optimal timing, frequency, and content of such interventions alongside OMMs remain unclear. Because obesity is chronic and OMMs are costly, pre-treatment programs may precede pharmacotherapy, though this can limit access and reinforce stigma. During treatment, lifestyle approaches can mitigate medication-related effects and enhance health beyond weight loss, addressing concerns such as inadequate nutrition or muscle loss through protein intake and physical activity and reducing gastrointestinal side effects via dietary strategies. After discontinuation, behavioral programs may help prevent weight regain and sustain health improvements. Tailoring lifestyle interventions to modern pharmacotherapy offers an opportunity for health-centered, patient-focused obesity care.</p>