<p>Marginalization of Indigenous peoples (IP) and increasing recognition of IPs’ roles in sustainable development have heightened interventions targeting these communities. The associated changes and consequences of development interventions on communities need to be understood to avoid reinforcing vulnerabilities and ensure that these do not counter intended outcomes. This paper analyzed the multidimensional changes in community well-being and the consequences of interventions on IP beneficiaries of the Philippine government’s conditional cash transfer program (<i>Pantawid Pamilyang Pilipino</i> Program). The qualitative descriptive study was done in nine purposively selected IP communities in the country. Data gathered through focus group discussion-workshops reveal that there were changes in well-being across five areas essential for sustainable livelihoods: environment, livelihood, community, IP culture, and gender status and roles. These intersecting changes are cumulatively driven by interventions, policies, and IP communities’ integration in the mainstream economy and culture. Positive and intended, as well as negative and unintended, consequences emanate from these changes. Understanding the intersectionality of intended and unintended social and environmental changes and the historical marginalization of IPs is important to engage communities effectively, catalyze positive outcomes, and foster sustainability. To facilitate culturally-relevant initiatives that holistically enhance well-being, it is recommended to: (1) co-design interventions using a human ecological systems perspective and learning approach, and (2) ground an intervention’s Theory of Change in the IP community’s change perspective. Such approaches can amplify the role of IPs as change agents charting towards their self-determined vision of sustainable development. The role of universities through community-engaged scholarship is also recognized.</p>