Home-based psychotherapy has expanded in the mental health community; however, little was known about the therapists' comfort level in a home-based venue. The purpose of this quantitative study was to assess therapists' comfort level (TCL) in providing psychotherapy in a home-based setting and how therapeutic competency (TC), therapeutic relationship (TR), and advanced therapeutic training (ATT) related to the comfort level. The social-ecological systems theory and the theory of comfort served as the theoretical frameworks. The present study used the Therapist Comfort Scale, Counseling Competencies Scale-Revised, the Scale to Assess Therapeutic Relationship in Community Mental Health Care-Clinician, and a demographic questionnaire. A multiple linear regression and correlational analysis were conducted to assess the predictive relationships among the variables. The participants were 76 therapists who provided psychotherapy in a home-based setting. The results revealed a statistically significant positive relationship between TCL and TR. This finding indicated that as the TR score increased, TCL also increased. There was a statistically significant positive relationship between TCL and TC, which indicated that as the TC score increased, TCL also increased. There was a statistically significant positive relationship between TCL and ATT, which indicated that as the ATT score increased, TCL also increased. It was hoped that this study's findings can serve to inform and guide the home-based psychotherapists to improve their therapeutic relationship. Once the therapeutic relationship is formed, the therapists will obtain a high level of comfort in discussing concerns openly with the patients, and parents/caregivers. In addition, when therapists reach a high level of comfort, it could make a positive difference in the patients' treatment outcomes. Thus, the findings of this study initiated positive social change at the level of the individual home-based therapist as well as to the vulnerable population that they serve.