For decades science educators and instructors focused on students' ability to memorize, retain, and recall scientific information precisely. Today's generation of educators emphasizes the educational environments that encourage academic and emotional learning of students that lead to greater academic success. Literature on education and development of first-generation students (FGS) suggests that further research continue to study conditions for which academic achievement of these students occurs, and what factors allow them to thrive (Demetriou et al., 2017). Stephens et al. (2012), provide additional evidence for how a university's cultural standards influence and affect first-generation students' college experiences (Stephens, Fryberg, Markus, Johnson, & Covarrubias, 2012). A primary purpose of this sequential explanatory mixed-methods study is to identify and assess specific educational contributions and factors critical in developing science self-efficacy in FGS, collecting first quantitative data and followed with subsequent qualitative analyses. The quantitative data consisted of pre-, mid-, and post-test data measuring science self-efficacy. The qualitative phase used a theoretical framework established by Quinlan (2016) which emphasizes the use of students' emotions in the development of four key relationships, namely students with: (a) instructor, (b) subject matter, (c) other students, and (d) their developing selves. The results of this study determined that understanding the learning needs of students, employing high-impact instructional methods, practicing compassionate pedagogy, and fostering critical relationships for FGS, contributed to students' learning needs, science self-efficacy and course success. Findings from this study also indicate that FGS are continuing to develop and understand their science self-efficacy and for which academic and classroom experiences influence their educational achievement. The relationship of the instructor in having positive interactions with the students, understanding that students acknowledge their emotions when learning, and that both FGS and Non-FGS narrated their emotional experiences when learning college biology, demonstrates that science self-efficacy continues to develop regardless of college generational status. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://bibliotheek.ehb.be:2222/en-US/products/dissertations/individuals.shtml.]