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Objectives: This study investigated the effects of outpatient rehabilitation therapy (RT) on the functional performance of children from Eastern Taiwan with rare or genetic diseases. Materials and Methods: This retrospective observational cohort study included 73 children from Eastern Taiwan who were affected with rare or genetic diseases, with an average age of 8.57 ± 5.33 years (47 boys and 26 girls). Each child received the goal-directed therapy known as outpatient RT, which was delivered by a multidisciplinary team of specialists. To assess the effectiveness of RT, the WeeFIM-C questionnaire data were collected and analyzed. Results: After receiving outpatient RT, most of the children only required low-to-moderate assistance with self-care tasks (4.36 ± 2.38), and they could perform mobility-related activities under supervision or independently (5.70 ± 2.29). Moreover, most only required minimal assistance with tasks related to cognitive functioning and tended to complete such tasks under supervision (4.97 ± 2.05). The functional performance was significantly different among three studied groups, in terms of self-care (F[2, 68] = 5.42, P < 0.007), mobility (F[2, 68] = 8.17, P < 0.001), cognitive functioning (F[2, 68] = 3.31, P < 0.042), and overall (F[2, 68] = 6.44, P < 0.003) functional performance. Conclusion: The results of this study demonstrated that the functional status was different among three studied groups in terms of self-care, mobility, and cognitive functioning after receiving outpatient RT.