Barriers to equity, diversity, and inclusion remain in Science, Technology, Engineering, and Mathematics (STEM) for historically underrepresented and marginalized individuals. The purpose of this study was to explore the experiences of women and LGBT+ academics and PhD students in the United Kingdom. Specifically, this article examines systemic challenges and support that 82 participants who identified as women and/or LGBT+ academics and PhD students have experienced in their STEM environments and throughout their careers. In this qualitative study, we employed intersectionality theory to frame a thematic analysis of interviews and focus groups. Our findings indicate that the experiences of participants are characterized more by inequities than by support from colleagues, peers, and higher education institutions. Inequities are widespread and intersectional, and have a cumulative impact whenever individuals endure multiple and potentially escalating challenges--which include hard-to-spot disadvantages, stereotypes, prejudice, as well as harassment, bullying, and discrimination. Participants' accounts illustrate the benefits of different support mechanisms but also the limitations of initiatives to support marginalized individuals and groups in STEM that are not systematically embedded across institutions. Based on our findings, we present two conceptual models to better understand systemic challenges and their consequences for women and LGBT+ academics and PhD students in STEM, as well as to inform more holistic support mechanisms to create more inclusive STEM environments. Implications from the study highlight institutional accountability as key to improving climates and transformative change.