The integration of pharmacotherapy with psychosocial interventions has an important role to play in the improvement of functional outcome of subjects with schizophrenia (SCZ), in all stages of the disorder. It is essential for the adequate management of unmet therapeutic needs, such as negative symptoms and cognitive dysfunctions which account for most of the functional impairment of subjects with SCZ and do not respond to available antipsychotics. Enhancing the knowledge on factors involved in the effectiveness of integrated treatment plans is an important step forward for SCZ care. This review aims to identify factors that might influence the impact of integrated treatments on functional outcome. Most studies on the impact of psychosocial treatments on functional outcome of subjects with SCZ did not control for the effect of prescribed antipsychotics or concomitant medications. However, several factors relevant to ongoing pharmacological treatment might influence the outcome of integrated therapy, with an impact on the adherence to treatment (e.g., therapeutic alliance and polypharmacotherapy) or on illness-related factors addressed by the psychosocial interventions (e.g., cognitive dysfunctions or motivational deficits). Indirect evidence suggests that treatment integration should consider the possible detrimental effects of different antipsychotics or concomitant medications on cognitive functions, as well as on secondary negative symptoms. Cognitive dysfunctions can interfere with participation to an integrated treatment plan and can be worsened by extrapyramidal or metabolic side effects of antipsychotics, or concomitant treatment with anticholinergics or benzodiazepines. Secondary negative symptoms, due to positive symptoms, sedation, extrapyramidal side effects or untreated depression, might cause early drop-out and poor adherence to treatment. Researchers and clinicians should examine all the above-mentioned factors and implement appropriate and personalized integrated treatments to improve the outcome of SCZ.