Lung cancer, as the leading cause of death in oncology is one of the most challenging diseases nowadays. Even after the implementation of checkpoint inhibitors and targeted therapy as a standard of therapy for metastatic disease, the chemotherapy backbone remains essential in the treatment of these patients. This study aimed to evaluate how administration particularities in chemotherapy and toxicity management can influence the outcome. We conducted a retrospective single-institution study, at Elias University Emergency Hospital, Bucharest, Romania, between 2014 and 2018, in a heterogeneous patient population with metastatic non-small cell lung cancer that received combination chemotherapy. The inclusion criteria for this trial were—histological proof of non-small cell lung cancer (NSCLC), stage IV disease, ECOG (Eastern Cooperative Oncology Group) performance status of a maximum of two, treatment with cytotoxic chemotherapy for at least four courses (patients with fewer courses were excluded). All patients received combination chemotherapy. The main focus was on the effect of dose reduction and treatment delay on overall survival and progression-free survival. A total of 129 patients were enrolled. The response rate in the studied population was 69% and 62.8% had no toxicity greater than grade 2. Chemotherapy regimens used had the following distribution—paclitaxel + carboplatin 41.9%, paclitaxel + carboplatin + bevacizumab 12.4%, pemetrexed + carboplatin 12.4%, gemcitabine + carboplatin 26.4% and other regimens 7%. Mean PFS (Progression Free Survival) was 9.1 months and the mean OS (Overall Survival) was 14 months. OS was not significantly different in the treatment delay group versus the no delay one, p < 0.25 but dose- reduction significantly impacted OS, p < 0.03. Administration particularities, like febrile neutropenia prophylaxis, treatment of chemotherapy-related anemia, respecting the details of chemostability and preparation rules and emesis prophylaxis, were considered reasons for the good outcome. Details regarding cytotoxic chemotherapy administration remain of paramount importance for a good outcome and the benefit for survival they convey is crucial. Sometimes the benefit the patient derives from these details is comparable to the one newer therapies convey.