The predictors of teacher motivation and job satisfaction on overall teacher well-being indicate significant relationship and well documented. However, majority of the studies have been conducted in high-income countries. The purpose of the systematic review is to assess the relationship between motivation and job satisfaction among teachers. This study used the SLR method; a literature search was conducted on Scopus and Google Scholar in the period decades range of 2020–2024 in relationship with the diverse socioeconomic and cultural contexts of the Global South. The results shown on Scopus and Google Scholar are n = 79 and n = 632, respectively. After PRISMA analysis, n = 55 studies were included in the review under Global South countries such as Malaysia, Indonesia, the Philippines, Brunei, and Thailand. A systematic literature review revealed that teachers experience moderate to high levels of mental health challenges, including stress, anxiety, depression, and burnout. Psychological well-being can be enhanced through positive attitudes, spiritual conviction, good support systems, personal growth, and a sense of responsibility. Intrinsic and extrinsic motivation and job satisfaction play critical roles in improving teacher performance, commitment, and competencies. These findings highlight strategies to sustain teacher well-being, offering insights for educational systems to foster support, reduce burnout, enhance teacher retention, and create a more positive learning environment. Future efforts should prioritize providing modern resources and improved school facilities while offering competency-based training programs to enhance teachers’ skills and efficiency. Managing workloads through digital transformation can further support teachers by streamlining tasks, boosting morale, fostering respect, and promoting overall well-being. These initiatives are crucial for ensuring teacher retention and satisfaction.