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(1) Background: Exon 20 insertion mutations (ex20ins) in <i>EGFR</i> and <i>HER2</i> are uncommon driver mutations in non-small-cell lung cancer (NSCLC), with a poor prognosis and few targeted therapy options, and there are limited real-world data. Here, we report the clinicopathologic features and outcomes for patients with ex20ins NSCLC across British Columbia, Canada. (2) Methods: NSCLC patients with ex20ins in <i>EGFR</i> or <i>HER2</i> were identified via tumour testing between 1 January 2016 and 31 December 2021 (n = 7233). Data were collected by chart review. Survival analyses were performed using the Kaplan–Meier method using the log-rank test. (3) Results: A total of 131 patients were identified. The median age was 66. Thirty-three percent of patients had brain metastases. For the <i>EGFR</i> cohort, the median OS was 18.6 months for patients who received any systemic therapy (ST) vs. 2.6 months for patients who did not (<i>p</i> < 0.001). Median OS was similar for patients treated with ex20ins-specific tyrosine kinase inhibitors (TKIs) vs. other STs (18.6 vs. 15.9 months; <i>p</i> = 0.463). The median first-line PFS was 4.1 vs. 7.4 months for patients treated with a TKI vs. other ST (<i>p</i> = 0.744). For the <i>HER2</i> cohort, the median OS was 9.0 months for patients who received any ST vs. 4.9 months for patients who did not (<i>p</i> = 0.015). The median OS was 23.0 months for patients treated with an ex20ins TKI vs. 5.6 months for patients who were not (<i>p</i> = 0.019). The median first-line PFS was 5.4 vs. 2.1 months for patients treated with a TKI vs. other ST (<i>p</i> = 0.343). (4) Conclusions: Overall survival was significantly longer among ex20ins patients who received any systemic therapy vs. those who did not. Overall survival was significantly better among <i>HER2</i> ex20ins patients who received ex20ins-specific TKIs.