It is important to gain more insight into specific subgroups of homeless young adults (HYA) to enable the development of tailored interventions that adequately meet their diverse needs and to improve their quality of life. Within a heterogeneous sample of HYA, we investigated whether subgroups are distinguishable based on risk- and protective factors for quality of life. In addition, differences between subgroups were examined regarding the socio-demographic characteristics, the use of cognitive coping strategies and quality of life. A total of 393 HYA using shelter facilities in the Netherlands were approached to participate, between December 2011 and March 2013. Structured face-to-face interviews were administered approximately 2weeks after shelter admission by trained research assistants. A latent class analysis was conducted to empirically distinguish 251 HYA in subgroups based on common risk factors (former abuse, victimisation, psychological symptoms and substance use) and protective factors (resilience, family and social support and perceived health status). Additional analysis of variance and chi-square tests were used to compare subgroups on socio-demographic characteristics, the use of cognitive coping strategies and quality of life. The latent class analysis yielded four highly interpretable subgroups: the at-risk subgroup, the high-risk and least protected subgroup, the low-risk subgroup and the higher functioning and protected subgroup. Subgroups of HYA with lower scores in risk factors showed higher scores in protective factors, the adaptive cognitive coping strategies and quality of life. Our findings confirm the need for targeted and tailored interventions for specific subgroups of HYA. Social workers need to be attentive to the pattern of risk- and protective factors in each individual to determine which risk factors are prominent and need to be targeted and which protective factors need to be enhanced to improve the quality of life of HYA.