The retirement phase is an opportunity to integrate healthy (nutrition/exercise) habits into daily life. We conducted this systematic review to assess which nutrition and exercise interventions most effectively improve body composition (fat/muscle mass), body mass index (BMI), and waist circumference (WC) in persons with obesity/overweight near retirement age (ages 55–70 y). We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials, searching 4 databases from their inception up to July 12, 2022. The NMA was based on a random effects model, pooled mean differences, standardized mean differences, their 95% confidence intervals, and correlations with multi-arm studies. Subgroup and sensitivity analyses were also conducted. Ninety-two studies were included, 66 of which with 4957 participants could be used for the NMA. Identified interventions were clustered into 12 groups: no intervention, energy restriction (i.e., 500–1000 kcal), energy restriction plus high-protein intake (1.1–1.7 g/kg/body weight), intermittent fasting, mixed exercise (aerobic and resistance), resistance training, aerobic training, high protein plus resistance training, energy restriction plus high protein plus exercise, energy restriction plus resistance training, energy restriction plus aerobic training, and energy restriction plus mixed exercise. Intervention durations ranged from 8 wk to 6 mo. Body fat was reduced with energy restriction plus any exercise or plus high-protein intake. Energy restriction alone was less effective and tended to decrease muscle mass. Muscle mass was only significantly increased with mixed exercise. All other interventions including exercise effectively preserved muscle mass. A BMI and/or WC decrease was achieved with all interventions except aerobic training/resistance training alone or resistance training plus high protein. Overall, the most effective strategy for nearly all outcomes was combining energy restriction with resistance training or mixed exercise and high protein. Health care professionals involved in the management of persons with obesity need to be aware that an energy-restricted diet alone may contribute to sarcopenic obesity in persons near retirement age.This network meta-analysis is registered athttps://www.crd.york.ac.uk/prospero/as CRD42021276465.