Climate change and flooding in Asian cities pose great challenges to the environmental and human security of the population and their governance systems. This paper examines the intersections of ecological-environmental and social vulnerability and the adaptive responses of urban poor communities and commercial-industrial establishments in Metro Manila to floods and other climate change-related effects, such as storm surges and sea-level rise (SLR). These weaken the communities’ ecological-environmental systems, threaten the well-being and security of the people and strain the resources of city governments. Disaggregating the ecological-environment vulnerabilities of a city/community according to specific places/spaces (or place-based vulnerabilities) that lead also to variable patterns among different groups (e.g., gender, income group, sector) of adaptive responses to flooding. Drawing a systematic sample of urban poor households and industrial-commercial establishments along the Pasig-Marikina River Basin of Metro Manila, this study utilised household surveys, key informant interviews, focus group discussions (FGD) and secondary data sources, in analysing the sources of their vulnerability and adaptive responses. Existing studies generally focus on the vulnerability and adaptation of urban-rural populations and do not highlight the interaction of place-based vulnerabilities with sector-specific vulnerabilities that reconfigure flood impacts and responses among the urban poor communities and commercial-industrial establishments during and after floods. In particular, poor and female-headed households residing in highly degraded environments or places/spaces within and across urban poor communities suffered higher damages and losses compared to better-off households and establishments. The interaction of these drivers of vulnerability further heightens and compromises the environmental and human security needs of poor people, their communities and those in the private sector that local/national government agencies need to respond.