In previous centuries, hospitals placed great emphasis on holistic approaches to healthcare, encompassing not only the medical treatment of disease but also patients’ psychological well-being and sense of belonging. However, the advancement of contemporary construction technologies has diminished the focus on a holistic approach. Recent modern hospitals have prioritised disease treatment over the human aspect of healing, neglecting the significance and profound influence of a healthy and aesthetically pleasing interior-built environment on patients’ health, sense of well-being, and broader societal and ecologically connected factors. This has led to an increased isolation from nature and a growing sense of ‘placelessness’, as Orr (1999) describes. Accordingly, research recommends that it is beneficial to incorporate nature and its elements into interior spaces, also referred to as the ‘biophilic approach’ (Ulrich 1983; Wilson 1984; Kellert et al. 2008; Zhong et al. 2022; McGee et al. 2022). The biophilic approach was first empirically described by Heerwagen and Hase (2001) and later developed into a systematic matrix by Kellert et al. 2008. Various initiatives have emerged to construct a biophilic matrix that aims to put the biophilic approach into practice. Nonetheless, these matrices have been unsuitable and have hampered the clarity of implementation procedures in the hospital’s interior environment. This paper aims to develop a new biophilic matrix that is suitable for oncology hospital interior design, with a specific focus on the chemotherapy department. The objective is achieved by conducting a systematic literature review of published biophilic matrices between 2001 and October 2023. The findings from the systematic literature review are then analysed and evaluated using a sophisticated mixed methodological framework: ‘A. What advancements have already been made to the existing matrix? B. What are the challenges when utilising the existing biophilic matrices in oncology hospitals? C. How can we adapt the existing biophilic matrices for implementation into the interior design of oncology hospitals?’ The result of this research is a new matrix specifically designed for hospital interior design and applicable for implementation, especially in the chemotherapy department.