Pandemics are stressful times, full of uncertainty and fear. During the COVID-19 pandemic, many Americans have experienced feelings of stress, grief, and loss. How Right Now (HRN)–and its Spanish-language counterpart, Qué Hacer Ahora (QHA)–is an evidence-based, culturally-relevant communication campaign designed to promote and strengthen the emotional well-being and resiliency of populations adversely affected by the COVID-19 pandemic and beyond. Developed by the Centers for Disease Control and Prevention (CDC) with support from the CDC Foundation, the campaign aims to help all Americans but has a specific focus on some of the disproportionately affected groups, including adults over 65 and their caregivers, individuals with pre-existing physical and mental health conditions, people experiencing violence, and those experiencing economic distress. Based on rapid, but robust, formative research, HRN offers audience-centric messages representing the real, everyday experiences and emotions that these audiences are having and addresses them in actionable ways. These include messages that address the social and structural barriers that disproportionately-affected groups have been facing long before the pandemic—and which are felt more acutely now. This paper provides an overview of the rapid, mixed-method, culturally-responsive formative research process undertaken to inform the development of HRN. Specifically, it describes how HRN’s disproportionately-affected audiences describe and discuss their emotional well-being during COVID-19 through the lens of Social Determinants of Health (SDOH). We introduce a secondary theory, Vital Conditions for Health and Well-Being (VCHW), which conceptualizes holistic well-being and the conditions that give rise to it and identifies levers for community change and improvement. Data collection methods included an environmental scan (n ≥ 700 publications); social listening (n ≥ 1 million social media posts); partner needs-assessment calls (n = 16); partner-convened listening sessions with community members (n = 29), online focus groups (n = 10), and a national probability survey (n = 731), all in English and Spanish. Findings suggest that HRN’s priority audiences’ emotional well-being and SDOH are interconnected. Disruptions in SDOH due to the COVID-19 pandemic can lead to emotional well-being challenges, eg, anxiety, for HRN’s priority audiences. While some disruptions may lead some people to adapt, connect with others, and be more resilient, there is a disparate impact of emotional well-being amid COVID-19 for those already experiencing disparities linked to SDOH. Understanding the perspectives and experiences of disproportionately affected populations through the lens of SDOH is vital to identifying the kinds of supports and services–like How Right Now/Qué Hacer Ahora–required for these populations.