Background: Self-esteem is an individual's subjective judgment of their own self-worth, which includes views of self-respect, confidence, and positive or negative self-image. Home-based vocational skill training consists of structured programs designed to provide relevant and marketable skills that may be learned and utilized at home. These programs provide technical knowledge and hands-on training in a variety of trades or topics, encouraging individuals to advance their livelihoods or seek entrepreneurial opportunities. This strategy flourishes in an economic environment which acknowledges human worth and believes in every individual's capacity to advocate for their own well-being through occupation. This project intends to improve self-esteem through home-based vocational skill training among transgenders with low self-esteem. Objective: The study aims to determine the Effect of Home-based Vocational skill training to improve self-esteem among transgenders with low self-esteem. Materials and Methods: This was a quasi-experimental study, conducted in Chennai, India, that included thirty transgender participants with low self-esteem, who were divided into two groups: a control group (n=15) and an experimental group (n=15). Participants were aged between 20 and 35 years. The participants in the experimental group received home-based vocational skill training for 45 minutes in each session (3 sessions per week) for about 3 months. They received training for approximately 36 sessions. Meanwhile, the participants in the control group received their conventional occupational therapy for the same duration. The pre-test and post-test scores of the transgenders in both the groups were assessed using Rosenberg's self-esteem scale. Data analysis was analyzed using the Mann-Whitney U test and Wilcoxon signed-rank test. Results: The results indicated statistically significant differences between the control and experimental groups (p-value < 0.05). Specifically, the experimental group exhibited a more substantial improvement in self-esteem compared to the control group. The Rosenberg Self-Esteem Scale scores revealed that the control group's mean score was 13.13, whereas the experimental group's mean score was 19.07, with a p-value of 0.00*, following the 12-week training program. Conclusion: From this study, it was concluded that the Home-Based Vocational Skill Training was effective to improve self-esteem among transgenders with low self-esteem.