Aims After heart transplantation (HTx), increments in physical activity (PA) are strongly recommended. However, participation rates in exercise-based cardiac rehabilitation and engagement in PA are insufficient in many patients. Hence, this study aimed to explore the central factors and the interconnections among distinct types of motivation to exercise, PA, sedentary time, psychosomatic, diet, and activity limitation characteristics in post-HTx patients. Methods and results This is a cross-sectional study involving 133 post-HTx patients (79 men, mean age 57 +/- 13 years, mean time from transplantation 55 +/- 42 months) recruited from an outpatient clinic in Spain. The patients were asked to fill in questionnaires measuring self-reported PA, motivation to exercise, kinesiophobia, musculoskeletal pain, quality of sleep, depression, functional capacity, frailty, sarcopenia risk, and diet quality. Two network structures were estimated: one network including PA and one network including sedentary time as nodes. The relative importance of each node in the network structures was determined using centrality analyses. According to the strength centrality index, functional capacity and identified regulation (subtypes of motivation to exercise) are the two most central nodes of the network (strength: z-score = 1.35-1.51). Strong and direct connections emerged between frailty and PA and between sarcopenia risk and sedentary time. Conclusion Functional capacity and autonomous motivation to exercise are the most promising targets of interventions to improve PA levels and sedentary time in post-HTx patients. Furthermore, frailty and sarcopenia risk were found to mediate the effects of several other factors on PA and sedentary time.