International studies have suggested that parental loss is a risk factor for poor physical and mental health, but all orphans do not develop the same kind and intensity of wellbeing indicators. This disparity is associated with certain biopsychosocial characteristics of the developing orphan which may interact with certain environmental factors to determine the levels of vulnerability a child may experience following parental death. While studies have been devoted to orphanhood in Ghana, no study has examined the nature of multisystemic risks within the sociocultural environment, and the factors within orphans which may interact to determine their experiences and developmental outcomes in Ghana. In the present paper, the Ecological Systems Theory is used to depict different vulnerabilities associated with orphanhood in the Ghanaian context. Using this theory, I demonstrate that Ghanaian orphans may experience vulnerabilities at all systems of the theory. Implications of the identified vulnerabilities for research, interventions and policy making are discussed.