Schistosomiasis japonica remains a public health concern in many areas of the Philippines. Periodic Mass Drug Administration (MDA) to at-risk populations is the main strategy for morbidity control of schistosomiasis. Attaining MDA coverage targets is important for the reduction of morbidity and prevention of complications due to the disease, and towards achieving Universal Health Care. The study employed a qualitative case study design. Key informant interviews and focus group discussions were conducted to provide in-depth and situated descriptions of the contexts surrounding the implementation of MDA in two selected villages in known schistosomiasis-endemic provinces in Mindanao in the Philippines. Data analysis was done using the Critical Ecology for Medical Anthropology (CEMA) model coupled with the intersectionality approach. It was found that within various areas in the CEMA model, enabling as well as constraining factors have been encountered in MDA in the study settings. The interplay of income class, geographical location, gender norms and faith-based beliefs may have led to key populations being missed during the conduct of MDA in the study sites. The constraints faced by the target beneficiaries of MDA, as well as programme implementers, must be addressed to enhance service delivery and to control morbidity due to schistosomiasis. Improving compliance with MDA also requires a holistic, integrated approach to addressing barriers to participation, which are shaped by wider socio-political and power structures.