Substance use among pregnant women is a perennial problem in the Western Cape Province of South Africa. There are many influential elements related with substance use among women of childbearing-age. Factors associated with substance use during pregnancy were explored using qualitative research approach and bio-ecological theoretical framework was utilised to guide the study. Participants were selected using purposive sampling. Participants accessed from the Department of Social Development who met the inclusion criteria of the study were interviewed using semi structured interviews. Participants were referred for psychological intervention during the interview if deemed necessary. Braun and Clarke’s six phases of thematic analysis were used to analyse the data. The study adhered to ethical measures for the participants’ protection. Participants had been knowledgeable about the study earlier than the initiation of the interviews and the important points of their voluntary participation had been explained. The key findings from this study illustrate that social factors, individual area and romantic relationship are the major contributing factors to substance use among pregnant ladies in this sample. Recommendations arising from the study encompass that the stakeholders, rehabilitation centers, Department of Health and future researchers ought to act proactively against substance use all through pregnancy.