Cardiometabolic non-communicable diseases (NCD) and their major risk factors are associated with adverse acute and chronic health outcomes and may pose risks to flight safety and economic burden. Restorative sleep, healthy nutrition, and sufficient physical activity are powerful lifestyle behaviours that are fundamental for human health and well-being, and each are independently associated with NCD risk reduction. Although occupational preventive medicine research is increasing, airline pilots are largely underrepresented in the literature. Through a series of seven studies, this PhD thesis aimed to enhance the understanding of modifiable health risk factor status for airline pilots and to investigate evidence-based strategies for promoting positive health, wellness, and NCD risk factor mitigation among airline pilots. To identify priority health risks among airline pilots and to serve as a foundation for further studies within the thesis, Study One systematically explored the global literature pertaining to the prevalence of cardiometabolic health risk factors among airline pilots. Study Two investigated the prevalence and distribution of subjective and objective cardiometabolic health risk factors among New Zealand airline pilots and compared these with the general population. Study Three synthesised global literature and summarised evidence-based considerations regarding the health benefits of sleep hygiene, healthy eating, and physical activity for cardiometabolic health promotion in airline pilots and further discussed evidence-based considerations for enhancing health behaviours in this occupational group. Study Four evaluated the efficacy of a 17-week, three-component personalised sleep, healthy eating, and physical activity lifestyle intervention for enhancing self-report health parameters during the coronavirus disease 2019 (COVID-19) pandemic. Subsequently, Study Five performed a 12-month follow-up investigation of the longitudinal effects of the 17-week intervention on self-report health parameters in addition to body mass and blood pressure management. Study Six further evaluated the effects of the three-component lifestyle intervention with utilisation of a wider range of objective cardiometabolic health parameters. Finally, Study Seven evaluated the efficacy of a smartphone-based app delivery of the three-component lifestyle intervention as a potentially scalable strategy for enhancing health and fitness parameters in airline pilots. In Study One, A total of 47 studies derived from 20 different countries among a total pooled sample of 36,454 airline pilots were reviewed. The systematic review revealed substantial prevalence of > 50% for overweight and obesity, insufficient physical activity, and elevated fatigue among airline pilots globally. Further, this study highlighted the heterogeneity in methodology and lacking quality and quantity among the current literature pertaining to airline pilots, identifying the need for further research to better understand health risk factors and risk factor mitigation strategies among airline pilots. In Study Two, the cross-sectional comparison of health risk factor prevalence between airline pilots (n = 504) and the general population (n = 2,033) identified notable and similar health risk factor prevalence between groups, with elevated prevalence of short sleep, physical inactivity, ‘at risk’ for hypertension, and lower positive self-rated health among airline pilots. Accordingly, findings called for further research to examine targeted, cost-effective intervention methods for promoting healthy body weight, managing blood pressure, and enhancing health behaviours to mitigate the risks of occupational morbidity, medical conditions causing loss of license, medical incapacity, and to support flight safety. In Study Three, the narrative review outlined occupational health risks in airline pilots, summarised the evidence on health benefits of sleep hygiene, healthy eating, and physical activity as preventive medicine, and discussed evidence-based considerations for promoting health behaviours in this occupational group. In Study Four, 38 airline pilots completed an acute 17-week personalised sleep hygiene, healthy eating, and physical activity intervention which elicited significant improvements in sleep quality and quantity, fruit and vegetable intake, and moderate-to-vigorous physical activity compared to the control group and suggested that achieving health guidelines for these behaviours promoted positive mental and physical health. Study Five, provides further support that the personalised three-component lifestyle intervention can elicit and sustain long-term improvements in body mass and blood pressure management, health behaviours, and perceived subjective health in overweight and obese airline pilots and may support quality of life during an unprecedented global pandemic. In Study Six, further implementation of the personalised three-component lifestyle intervention among 67 overweight airline pilots elicited significant (p = < 0.001) positive change associated with moderate to large effects sizes for objective health measures (VO2max, body mass, skinfolds, girths, blood pressure, resting heart rate, push-ups, plank isometric hold) and self-report health (weekly moderate-to-vigorous physical activity, sleep quality and quantity, fruit and vegetable intake, and self-rated health) at 4-months post-intervention, relative to the control group (n = 58). Lastly, Study Seven utilised a randomised control trial design to deliver a smartphone-based app three-component lifestyle intervention among 94 airline pilots, which elicited positive changes associated with trivial to large effects sizes for objective health measures (Cooper’s 12-minute exercise test, resting heart rate, push-ups, plank isometric hold) and self-report health (weekly moderate-to-vigorous physical activity, sleep quality and quantity, fruit and vegetable intake, self-rated health, and perceived stress and fatigue) at 4-months post-intervention, relative to the control group (n = 92). In summary, the studies in this thesis provide a foundation for understanding cardiometabolic health risk factor prevalence among airline pilots. Furthermore, our series of controlled clinical trials provide preliminary evidence that a personalised three-component physical activity, healthy eating, and sleep hygiene intervention can elicit short-term improvements and may promote sustained long-term positive adaptations in objective and subjective health parameters in airline pilots. These findings are important for health care professionals and researchers to provide insight regarding the efficacy of lifestyle interventions for promoting health, and to inform practices relating to disease prevention, health promotion, and public health policy making. Furthermore, in relation to the limited literature base pertaining to health behaviour intervention research among airline pilots, our findings provide novel contributions to this field.