There are increased sector-wide efforts within health and social care systems to engage those with lived experience in service design, delivery, and monitoring - aiming to secure more equitable health outcomes. However, critical knowledge gaps persist around how national whole-system engagement strategies can account for the challenges experienced by populations that encounter exclusion within complex multi-layered systems. This includes a failure to delineate shared challenges across groups, and to develop transferable cross-group frameworks to assist sector-wide change. There is, therefore, a danger that those groups already least heard will be collectively left behind. With a view to informing a more inclusive engagement strategy in Ireland, this national study aims to investigate multi-level (policy and strategic, operational, on-the-ground services, individual) shared challenges impacting engagement for five populations who have been identified as underserved groups in a complex health and social care system, including: (1) those who misuse drugs and alcohol, (2) those who are experiencing homelessness, (3) those experiencing mental health, (4) migrants and those of minority ethnicies, and (5) Irish Travellers. Adopting a mixed-methods approach which draws on an evidence-informed multistakeholder perspective, this study employs data from: focus groups and life-course interviews with lived-experience populations (n=136), five focus groups (n=39) and a national on-line survey (n=320) with population-specific services providers; and national-level stakeholder interviews (n=9). Two cross-group participatory consultative forums with lived-experience and provider participants (n=28) were used to co-produce priority action areas based on study findings. This article presents findings on shared challenges in engaging these groups around leadership and commitment, implementation and action, population capacities, trust, and representation, stigma, and discrimination. Derived from these challenges, six development areas are presented to advance an inclusive equitable engagement approach in Ireland. These comprise: 1) balancing top-down prioritisation, and bottom-up direction; 2) sustaining multi-level, multi-form implementation; 3) measuring effectiveness and action; 4) embedding inclusive equitable engagement; 5) trust as a prerequisite, and outcome; and 6) an equalising, agency empowering agenda.