Cancer-related art therapy and fatigue can be examined in a multi-level framework in which the experience of fatigue is not merely a consequence of a decrease in physical energy, but is the result of complex interactions between neurological, emotional, cognitive, inflammatory, and social processes. Cancer-related fatigue is one of the most common symptoms in patients with cancer and even at some stages after treatment ends, and can significantly affect daily activity, social participation, feelings of independence, and quality of life. This type of fatigue does not usually resolve with simple rest and may be accompanied by physical weakness, sleep disturbances, decreased motivation, anxiety, depression, concentration problems, and feelings of psychological exhaustion. From a neurophysiological perspective, the experience of fatigue is the result of the interaction of brain networks related to emotion regulation, attention, motivation, effort perception, pain processing, and the body's automatic regulation, and therefore intervention in one of these pathways can affect the overall experience of fatigue. Art therapy is presented in this framework as an experimental psychological intervention that uses processes such as painting, drawing, collage, illustration, music, or other artistic practices to facilitate the expression of emotion, reduce tension, and promote psychological adjustment. The theoretical basis of this approach is based on the assumption that creative activity can organize the patient's internal experience through non-verbal pathways and allow for the processing of difficult emotions related to the disease, treatment, and the future. In cancer conditions, fatigue may be affected by inflammation, pain, sleep disturbances, hormonal changes, drug side effects, and anticancer treatments, as well as exacerbated by worry, frustration, fear of disease progression, and feelings of lack of control. From this perspective, art therapy is not intended to directly eliminate fatigue caused by medical factors, but can target a part of the psychophysiological cycle associated with it. One possible pathway is the effect of artistic activity on regulating emotional arousal and reducing perceived stress, because reducing stress can reduce the intensity of stress responses and physiological arousal. The autonomic nervous system is particularly important in this process, and the balance between sympathetic and parasympathetic activity can be related to feelings of calm, tension, heart rate, sleep quality, and the body's recovery capacity. Structured artistic activity, especially when combined with breathing, focused attention, and a supportive therapeutic environment, may facilitate a gradual transition from a state of arousal and worry to a calmer state. On the other hand, cognitive engagement with the creative process can divert the patient's attention from the continuous focus on physical symptoms and threatening thoughts for a period of time, creating a kind of reorientation of attention. This process can be analyzed in relation to neural networks involved in attention, cognitive control, emotion processing, and motivation, although the extent and direction of these effects depend on the type of artistic activity, individual characteristics, and the patient's clinical status. Research evidence in the field of artistic and psychosocial interventions in cancer has shown that art activities can be associated with a reduction in anxiety and psychological distress, improved mood, increased sense of participation, and improved quality of life in some groups of patients. In some researches, the reduction of psychological symptoms after art interventions can indirectly reduce the perception of fatigue, as anxiety and negative mood are factors affecting the severity of fatigue experience. Also, creating a sense of accomplishment in performing a creative activity can enhance the patient's self-efficacy and sense of empowerment and prevent the cycle of passivity, withdrawal, and decreased activity. The research background related to art therapy in cancer has mainly focused on outcomes such as anxiety, depression, quality of life, emotion regulation, pain, and psychological adjustment, and the study of fatigue from the perspective of an integrated neurophysiological model still requires more detailed and controlled studies. The importance of this issue lies in the fact that cancer fatigue is a multifactorial phenomenon and its analysis solely based on psychological or physical indicators cannot fully explain the complexity of the patient's experience. In the meantime, the relationship between fatigue and excitement is particularly important, as increased anxiety and rumination can increase the consumption of cognitive resources and the perception of effort, and in turn, reducing tension and improving emotion regulation may alter the experience of energy and functional capacity. Art therapy can help the patient make their emotional experience visible and processable by providing a safe space to express fear, anger, sadness, loss, and worry. Illustration and painting also make it possible to represent experiences that are sometimes difficult for the patient to express verbally. As a result, the artistic process can be transformed from a simple activity into a tool for meaning-making and organizing the experience of illness. From a cognitive perspective, active participation in artistic activity may increase a sense of control and agency, which may have been reduced in cancer due to the patient's dependence on treatment plans and physical limitations. Increased agency can be associated with greater participation in daily activities and better adaptation to the limitations of treatment. Art therapy can also be used in supportive care and psycho-oncology programs to simultaneously identify and manage psychological factors affecting fatigue. For example, the initial assessment can assess the severity of fatigue, sleep quality, pain, anxiety, depression, activity level, and therapeutic conditions, and then choose the type of artistic intervention based on individual needs. In patients with severe fatigue, short, low-intensity, flexible art activities may be more appropriate than long-term activities that require physical exertion. Adjusting the intensity and duration of activity is important, as the goal of art therapy is not to increase functional pressure on the patient, but to create a manageable, meaningful, and supportive experience. In hospital settings, individual or group art therapy sessions can be tailored to the patient's physical condition, stage of treatment, and preferences. In group sessions, in addition to the creative process, social support and reducing feelings of isolation may also help reduce the mental burden of illness. Quality of life in this model is an important end outcome, as the reduction in fatigue is only clinically meaningful when it also leads to improvements in functioning, social participation, mood, sleep, or life satisfaction. Therefore, the evaluation of the effectiveness of art therapy should not focus on a single indicator such as fatigue intensity and should rather include a set of physical, psychological, and functional indicators. The use of validated tools to measure fatigue related to cancer, quality of life, anxiety, depression, and sleep can allow for a more accurate assessment of the outcomes of the intervention. In future research, physiological indicators such as heart rate, heart rate variability, and some stress-related biomarkers can be investigated along with psychological measures to better clarify the relationship between subjective experience of fatigue and physiological changes. Despite the theoretical capacity of art therapy, there are also challenges that need to be considered in interpreting the results. Wide differences between types of cancer, stage of disease, type of treatment, severity of complications, age, social status, and personality traits of patients can cause heterogeneity in response to the intervention. Also, differences in the type of art, number of sessions, duration of intervention, therapist skill, and method of implementation of protocols make it difficult to compare the results of the studies. Some studies also reduce the possibility of definitive conclusions about the specific effect of art therapy on fatigue due to limited sample size, short follow-up period, or lack of a suitable control group. On the other hand, it is difficult to separate the effect of art therapy from the effect of supportive interaction with the therapist, presence in the group, attention received, and positive patient expectation of treatment. Therefore, in future research, it is necessary to use more controlled designs, larger samples, and longer follow-ups. A distinction must also be made between actual reduction in fatigue and changes in the perception of fatigue, as art therapy may first affect a person's subjective experience, emotion, and meaning of illness, and functional changes may appear later. Clinical application of this approach makes more sense when combined with medical care, appropriate physical activity, sleep management, pain management, nutritional support, and standard psychological interventions. In such a model, art therapy is part of a comprehensive psycho-oncological program that aims to reduce the psychological burden of illness, promote adaptation, and help maintain quality of life. Finally, the neurophysiological approach to art therapy suggests that cancer-related fatigue should be considered a phenomenon resulting from the interaction of the body, brain, emotion, and environment, and not merely a symptom of physical weakness. Artistic activity can affect part of this complex network through attention regulation, emotion processing, increased sense of agency, reduced perceived stress, and strengthening social connection, but determining the extent to which it directly affects fatigue requires stronger empirical evidence. Accordingly, the development of standardized, personalized, and based interventions based on the patient's physical and psychological needs can be an important path for future research and allow for a more precise link between neuroscience, health psychology, psycho-oncology, and art therapy.