This study is about the Sustainable Livelihood and Entrepreneurship Program for differently abled beneficiaries. Forty (40) physically challenged women, affected by a massive flooding in 2020, were selected by SPUP Community Development Center Foundation, Inc. (SPUP-CDCFI) from the University’s partner communities as recipients of the program. SPUP-CDCFI responded to their unique situation and crafted a special program relevant to their conditions and needs by promoting and developing their entrepreneurial skills towards quality of life and sustainable living. In a 10-month period, the recipients were provided with capacity building and empowerment activities. Through the United Nations Development Programme (UNDP) and the Department of Social Welfare and Development (DSWD), a start-up capital was also provided to each of the recipients. At present, the program beneficiaries are already engaged in sustainable livelihood through income generating activities ranging from culinary activities, weaving and handicraft making, ornamental, fruit and vegetable gardening, animal raising, and ambulant vending. The program has provided the recipients with livelihood that sustains their everyday life and welfare of their respective family. Moreover, the program developed their entrepreneurial skills and ushered in improvement in their socio-economic conditions through sustainable livelihood. It has also advanced their social skills and has fostered in them a positive outlook, and quality of life. This is one of the contributions of St. Paul University Philippines (SPUP) in empowering the differently abled persons in Cagayan to engage in self-employment activities and contribute to economic and social progress.